serpins

Summary

Summary: A family of serine proteinase inhibitors which are similar in amino acid sequence and mechanism of inhibition, but differ in their specificity toward proteolytic enzymes. This family includes alpha 1-antitrypsin, angiotensinogen, ovalbumin, antiplasmin, alpha 1-antichymotrypsin, thyroxine-binding protein, complement 1 inactivators, antithrombin III, heparin cofactor II, plasminogen inactivators, gene Y protein, placental plasminogen activator inhibitor, and barley Z protein. Some members of the serpin family may be substrates rather than inhibitors of SERINE ENDOPEPTIDASES, and some serpins occur in plants where their function is not known.

Top Publications

  1. ncbi Serpin structure, mechanism, and function
    Peter G W Gettins
    Department of Biochemistry and Molecular Genetics, University of Illinois at Chicago, M C 536, 1819 53 West Polk Street, Chicago, Illinois 60612, USA
    Chem Rev 102:4751-804. 2002
  2. pmc Visceral adipose tissue-derived serine protease inhibitor: a unique insulin-sensitizing adipocytokine in obesity
    Kazuyuki Hida
    Department of Medicine and Clinical Science, Okayama University Graduate School of Medicine and Dentistry, Okayama 700 8558, Japan
    Proc Natl Acad Sci U S A 102:10610-5. 2005
  3. ncbi SERPINB3, apoptosis and autoimmunity
    Laura Vidalino
    Clinica Medica 5, Department of Clinical and Experimental Medicine, University of Padua, Italy
    Autoimmun Rev 9:108-12. 2009
  4. pmc Novel scabies mite serpins inhibit the three pathways of the human complement system
    Angela Mika
    Infectious Diseases Program, Biology Department, Queensland Institute of Medical Research, Brisbane, Queensland, Australia
    PLoS ONE 7:e40489. 2012
  5. ncbi Serpin structure, function and dysfunction
    J A Huntington
    Department of Haematology, Cambridge Institute for Medical Research, University of Cambridge, Cambridge, UK
    J Thromb Haemost 9:26-34. 2011
  6. ncbi Innate immune responses of a lepidopteran insect, Manduca sexta
    Michael R Kanost
    Department of Biochemistry, Kansas State University, Manhattan, KS 66506, USA
    Immunol Rev 198:97-105. 2004
  7. ncbi Vaspin gene expression in human adipose tissue: association with obesity and type 2 diabetes
    Nora Kloting
    University of Leipzig, Department of Internal Medicine III, 04103 Leipzig, Germany
    Biochem Biophys Res Commun 339:430-6. 2006
  8. ncbi Serum vaspin concentrations in human obesity and type 2 diabetes
    Byung Soo Youn
    University of Leipzig, Department of Medicine, Ph Rosenthal Str 27, 04103 Leipzig, Germany
    Diabetes 57:372-7. 2008
  9. ncbi Circulating pigment epithelium-derived factor levels are associated with insulin resistance and decrease after weight loss
    Monica Sabater
    Department of Diabetes, Endocrinology, and Nutrition, Institut d Investigació Biomédica de Girona, Instituto de Salud Carlos III, Girona, Spain
    J Clin Endocrinol Metab 95:4720-8. 2010
  10. ncbi Vaspin serum concentrations in patients with carotid stenosis
    Gabriela Aust
    Center of Surgery, Department of Visceral, Transplantation, Thoracic, and Vascular Surgery, Medical Faculty, University of Leipzig, Leipzig, Germany
    Atherosclerosis 204:262-6. 2009

Detail Information

Publications303 found, 100 shown here

  1. ncbi Serpin structure, mechanism, and function
    Peter G W Gettins
    Department of Biochemistry and Molecular Genetics, University of Illinois at Chicago, M C 536, 1819 53 West Polk Street, Chicago, Illinois 60612, USA
    Chem Rev 102:4751-804. 2002
  2. pmc Visceral adipose tissue-derived serine protease inhibitor: a unique insulin-sensitizing adipocytokine in obesity
    Kazuyuki Hida
    Department of Medicine and Clinical Science, Okayama University Graduate School of Medicine and Dentistry, Okayama 700 8558, Japan
    Proc Natl Acad Sci U S A 102:10610-5. 2005
    ..These findings indicate that vaspin exerts an insulin-sensitizing effect targeted toward WATs in states of obesity...
  3. ncbi SERPINB3, apoptosis and autoimmunity
    Laura Vidalino
    Clinica Medica 5, Department of Clinical and Experimental Medicine, University of Padua, Italy
    Autoimmun Rev 9:108-12. 2009
    SERPINB3 (Squamous Cell Carcinoma Antigen, SCCA1) is a member of the ov-serpins, a serine protease inhibitors family expressed in many cell types including normal epithelium, leukocytes, tumors of epithelial origin and primary liver ..
  4. pmc Novel scabies mite serpins inhibit the three pathways of the human complement system
    Angela Mika
    Infectious Diseases Program, Biology Department, Queensland Institute of Medical Research, Brisbane, Queensland, Australia
    PLoS ONE 7:e40489. 2012
    ..Detailed functional analysis revealed that both serpins interfered with all three pathways of the human complement system at different stages of their activation...
  5. ncbi Serpin structure, function and dysfunction
    J A Huntington
    Department of Haematology, Cambridge Institute for Medical Research, University of Cambridge, Cambridge, UK
    J Thromb Haemost 9:26-34. 2011
    b>Serpins have been studied as a distinct protein superfamily since the early 80s...
  6. ncbi Innate immune responses of a lepidopteran insect, Manduca sexta
    Michael R Kanost
    Department of Biochemistry, Kansas State University, Manhattan, KS 66506, USA
    Immunol Rev 198:97-105. 2004
    ..Inhibitory regulation of the proteinases by serpins and association of the proteinase homologs with a bacteria-binding lectin are important for ensuring a localized ..
  7. ncbi Vaspin gene expression in human adipose tissue: association with obesity and type 2 diabetes
    Nora Kloting
    University of Leipzig, Department of Internal Medicine III, 04103 Leipzig, Germany
    Biochem Biophys Res Commun 339:430-6. 2006
    ..In conclusion, our data indicate that induction of human vaspin mRNA expression in adipose tissue is regulated in a fat depot-specific manner and could be associated with parameters of obesity, insulin resistance, and glucose metabolism...
  8. ncbi Serum vaspin concentrations in human obesity and type 2 diabetes
    Byung Soo Youn
    University of Leipzig, Department of Medicine, Ph Rosenthal Str 27, 04103 Leipzig, Germany
    Diabetes 57:372-7. 2008
    ..We have recently shown that vaspin mRNA expression in adipose tissue is related to parameters of obesity and glucose metabolism. However, the regulation of vaspin serum concentrations in human obesity and type 2 diabetes is unknown...
  9. ncbi Circulating pigment epithelium-derived factor levels are associated with insulin resistance and decrease after weight loss
    Monica Sabater
    Department of Diabetes, Endocrinology, and Nutrition, Institut d Investigació Biomédica de Girona, Instituto de Salud Carlos III, Girona, Spain
    J Clin Endocrinol Metab 95:4720-8. 2010
    ..We aimed to study circulating pigment epithelium-derived factor (PEDF) in vivo in association with insulin resistance and in vitro in human adipocytes...
  10. ncbi Vaspin serum concentrations in patients with carotid stenosis
    Gabriela Aust
    Center of Surgery, Department of Visceral, Transplantation, Thoracic, and Vascular Surgery, Medical Faculty, University of Leipzig, Leipzig, Germany
    Atherosclerosis 204:262-6. 2009
    ....
  11. pmc Constitutive overexpression of pigment epithelium-derived factor inhibition of ocular melanoma growth and metastasis
    Hua Yang
    Department of Ophthalmology, Emory University School of Medicine, Atlanta, Georgia 30322, USA
    Invest Ophthalmol Vis Sci 51:28-34. 2010
    ..This study investigates whether constitutive overexpression of PEDF inhibits the growth and hepatic micrometastasis of ocular melanoma...
  12. ncbi Role for DNA methylation in the control of cell type specific maspin expression
    Bernard W Futscher
    Department of Pharmacology and Toxicology, Bone Marrow Transplant Program, Arizona Cancer Center, The University of Arizona, Tucson, Arizona 85724, USA
    Nat Genet 31:175-9. 2002
    ..These findings indicate that cytosine methylation is important in the establishment and maintenance of cell type restricted gene expression...
  13. ncbi The paradoxical expression of maspin in ovarian carcinoma
    Anil K Sood
    Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, University of Iowa, University of Iowa Hospitals and Clinics, Iowa City, Iowa 52242 1109, USA
    Clin Cancer Res 8:2924-32. 2002
    ..These paradoxical results may offer new insights regarding the role of maspin in ovarian cancer progression that may also impact diagnosis and treatment strategies...
  14. pmc Overexpression of pigment epithelium-derived factor decreases angiogenesis and inhibits the growth of human malignant melanoma cells in vivo
    Riichiro Abe
    Department of Dermatology, Hokkaido University Graduate School of Medicine, Sapporo, Japan
    Am J Pathol 164:1225-32. 2004
    ..PEDF therefore might be a promising novel therapeutic agent for treatment of patients with melanoma...
  15. ncbi Characterization of PEDF: a multi-functional serpin family protein
    S Filleur
    Department of Urology, Texas Tech University Health Sciences Center, 3601 4th Street, MS 6591, Lubbock, Texas 79430 6591, USA
    J Cell Biochem 106:769-75. 2009
    ....
  16. pmc Interleukin-6 trans-signalling differentially regulates proliferation, migration, adhesion and maspin expression in human prostate cancer cells
    Frédéric R Santer
    Department of Urology, Innsbruck Medical University, Anichstrasse 35, A 6020 Innsbruck, Austria
    Endocr Relat Cancer 17:241-53. 2010
    ..Collectively, these data suggest that selective targeting of IL-6TS might allow to refine the currently available experimental anti-IL-6 therapies against PC...
  17. ncbi Conformational pathology of the serpins: themes, variations, and therapeutic strategies
    Bibek Gooptu
    School of Crystallography, Birkbeck College, University of London, London, UK
    Annu Rev Biochem 78:147-76. 2009
    ..Polymers of serpins can also form in extracellular tissues where they activate inflammatory cascades...
  18. pmc Identification of the antivasopermeability effect of pigment epithelium-derived factor and its active site
    Hua Liu
    Wilmer Ophthalmological Institute, Johns Hopkins Hospital, Baltimore, MD 21287 8984, USA
    Proc Natl Acad Sci U S A 101:6605-10. 2004
    ..Furthermore, PEDF may represent a superior therapeutic approach to sepsis-associated hypotension, nephrotic syndrome, and other sight-threatening and life-threatening diseases resulting from excessive vascular permeability...
  19. ncbi Identification of a lipase-linked cell membrane receptor for pigment epithelium-derived factor
    Luigi Notari
    National Eye Institute, National Institutes of Health, Bethesda, Maryland 20892, USA
    J Biol Chem 281:38022-37. 2006
    ....
  20. ncbi Maspin, a serpin with tumor-suppressing activity in human mammary epithelial cells
    Z Zou
    Division of Cancer Genetics, Dana Farber Cancer Institute, Boston, MA 02115
    Science 263:526-9. 1994
    ..Analysis of human breast cancer specimens revealed that loss of maspin expression occurred most frequently in advanced cancers. These results support the hypothesis that maspin functions as a tumor suppressor...
  21. ncbi Pigment epithelium-derived factor: a potent inhibitor of angiogenesis
    D W Dawson
    Department of Microbiology Immunology, Department of Pathology, Robert H Lurie Comprehensive Cancer Center, Northwestern University Medical School, Chicago, IL 60611, USA
    Science 285:245-8. 1999
    ..These results suggest that PEDF may be of therapeutic use, especially in retinopathies where pathological neovascularization compromises vision and leads to blindness...
  22. ncbi An immune-responsive Serpin regulates the melanization cascade in Drosophila
    Ennio De Gregorio
    Centre de Génétique Moléculaire du CNRS, 91198 Gif sur Yvette, France
    Dev Cell 3:581-92. 2002
    ..Our data demonstrate that Serpin-27A is required to restrict the phenoloxidase activity to the site of injury or infection, preventing the insect from excessive melanization...
  23. ncbi Pigment epithelium-derived factor suppresses ischemia-induced retinal neovascularization and VEGF-induced migration and growth
    Elia J Duh
    Department of Ophthalmology, Johns Hopkins University School of Medicine, Maumenee 809, 600 N Wolfe Street, Baltimore, MD 21287, USA
    Invest Ophthalmol Vis Sci 43:821-9. 2002
    ....
  24. ncbi Proinflammatory cytokines and angiogenic and anti-angiogenic factors in vitreous of patients with proliferative diabetic retinopathy and eales' disease
    Ponnalagu Murugeswari
    Department of Immunology, Dr G Venkataswamy Eye Research Institute, Aravind Medical Research Foundation, Tamilnadu, India
    Retina 28:817-24. 2008
    ....
  25. ncbi Pigment epithelium-derived factor (PEDF) is an endogenous antiinflammatory factor
    Sarah X Zhang
    Department of Medicine Endocrinology, Department of Cell Biology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, USA
    FASEB J 20:323-5. 2006
    ..These findings suggest that PEDF is a novel endogenous anti-inflammatory factor in the eye. The decrease of ocular PEDF levels may contribute to inflammation and vascular leakage in DR...
  26. pmc Pigment epithelium-derived factor regulates lipid metabolism via adipose triglyceride lipase
    Melissa L Borg
    Biology of Lipid Metabolism Laboratory, Department of Physiology, Monash University, Clayton, Victoria, Australia
    Diabetes 60:1458-66. 2011
    ..We used ATGL(-/-) mice to determine the role of PEDF in regulating lipid and glucose metabolism...
  27. ncbi Neuroserpin, a brain-associated inhibitor of tissue plasminogen activator is localized primarily in neurons. Implications for the regulation of motor learning and neuronal survival
    G A Hastings
    Department of Protein Therapeutics, Human Genome Sciences Inc, Rockville, Maryland 20850, USA
    J Biol Chem 272:33062-7. 1997
    ..Taken together, these data suggest that neuroserpin is likely to be a critical regulator of tPA activity in the central nervous system, and as such may play an important role in neuronal plasticity and/or maintenance...
  28. ncbi The axonally secreted serine proteinase inhibitor, neuroserpin, inhibits plasminogen activators and plasmin but not thrombin
    T Osterwalder
    Institute of Biochemistry, University of Zurich, Switzerland
    J Biol Chem 273:2312-21. 1998
    ..Thus, we postulate that neuroserpin could represent a regulatory element of extracellular proteolytic events in the nervous system mediated by plasminogen activators or plasmin...
  29. ncbi Down-regulated expression of SERPIN genes located on chromosome 18q21 in oral squamous cell carcinomas
    Masashi Shiiba
    Department of Clinical Molecular Biology, Graduate School of Medicine, Chiba University, Chiba City, Chiba 260 8670, Japan
    Oncol Rep 24:241-9. 2010
    b>Serpins (serine protease inhibitors) are known as a diverse family of protease inhibitors; however, various other biological activities including tumor suppression, have been recently reported for these molecules...
  30. pmc Neuroserpin, an axonally secreted serine protease inhibitor
    T Osterwalder
    Institute of Biochemistry, University of Zurich, Switzerland
    EMBO J 15:2944-53. 1996
    ..Thus, neuroserpin might function as an axonally secreted regulator of the local extracellular proteolysis involved in the reorganization of the synaptic connectivity during development and synapse plasticity in the adult...
  31. pmc Pigment epithelium-derived factor inhibits neointimal hyperplasia after vascular injury by blocking NADPH oxidase-mediated reactive oxygen species generation
    Kazuo Nakamura
    Department of Medicine, Division of Cardio Vascular Medicine, Kurume University School of Medicine, 67 Asahi Machi, Kurume 830 0011, Japan
    Am J Pathol 170:2159-70. 2007
    ..Our present study suggests that substitution of PEDF may be a novel therapeutic strategy for restenosis after balloon angioplasty...
  32. ncbi PEDF: anti-angiogenic guardian of ocular function
    Noel Bouck
    Dept of Microbiology Immunology and Robert H Lurie Comprehensive Cancer Center, Northwestern University Medical School, 310 East Superior Street, Chicago, IL 60611, USA
    Trends Mol Med 8:330-4. 2002
    ..The molecular basis for this delicate control of endothelial cells is beginning to be understood and strategies to test the ability of PEDF to ameliorate or prevent vessel damage in the eye are developing rapidly...
  33. ncbi Manduca sexta serpin-4 and serpin-5 inhibit the prophenol oxidase activation pathway: cDNA cloning, protein expression, and characterization
    Youren Tong
    Department of Biochemistry, Kansas State University, Manhattan, Kansas 66506, USA
    J Biol Chem 280:14923-31. 2005
    ..To investigate the roles of protease inhibitors in regulating this pathway, we cloned cDNAs for two new serpins (serpin-4 and serpin-5) from the tobacco hornworm, Manduca sexta...
  34. ncbi Circadian rhythm of serum vaspin in healthy male volunteers: relation to meals
    Eunheui Jeong
    Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, Pungnap 2 dong, Songpa Gu, Seoul 138 736, Korea
    J Clin Endocrinol Metab 95:1869-75. 2010
    ..Visceral adipose tissue-derived serine protease inhibitor (vaspin) is a novel adipokine with insulin-sensitizing effects. However, the physiological role for vaspin in human metabolic regulation remains to be established...
  35. ncbi Distinct melanization pathways in the mosquito Aedes aegypti
    Zhen Zou
    Department of Entomology and the Institute for Integrative Genome Biology, University of California, Riverside, Riverside, CA 92521, USA
    Immunity 32:41-53. 2010
    ..activation pathways carried out by different modules of serine proteases and their specific inhibitors serpins. Immune melanization proteases (IMP-1 and IMP-2) and Serpin-1 mediate hemolymph prophenoloxidase cleavage and ..
  36. ncbi In vitro and in vivo biological activity of PEDF against a range of tumors
    Matthew L Broadhead
    University of Melbourne, St Vincent s Hospital, Department of Orthopaedics and Surgery, L3, Daly Wing, 35 Victoria Pde, Fitzroy 3065, Vic, Australia
    Expert Opin Ther Targets 13:1429-38. 2009
    ..These direct and indirect effects of PEDF have been examined in vitro and in vivo for a range of malignancies...
  37. pmc Anti-tumor effect of adenovirus-mediated gene transfer of pigment epithelium-derived factor on mouse B16-F10 melanoma
    Li Ping Yang
    State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Clinical Medicine School, Sichuan University, Chengdu, Sichuan, PR China
    J Exp Clin Cancer Res 28:75. 2009
    ..As a potent inhibitor of tumor angiogenesis, pigment epithelium-derived factor (PEDF) has recently been studied and used as an anticancer agent in several tumor models...
  38. ncbi The ratio of VEGF/PEDF expression in bone marrow mesenchymal stem cells regulates neovascularization
    Wei Fan
    Institute of Health and Biomedical Innovation, Queensland University of Technology, Kelvin Grove Campus, Brisbane QLD 4059, Australia
    Differentiation 81:181-91. 2011
    ....
  39. pmc An overview of the serpin superfamily
    Ruby H P Law
    Department of Biochemistry and Molecular Biology, Monash University, Clayton Campus, Melbourne VIC 3800, Australia
    Genome Biol 7:216. 2006
    b>Serpins are a broadly distributed family of protease inhibitors that use a conformational change to inhibit target enzymes. They are central in controlling many important proteolytic cascades, including the mammalian coagulation pathways...
  40. pmc Tissue-type plasminogen activator induces opening of the blood-brain barrier via the LDL receptor-related protein
    Manuel Yepes
    Department of Vascular Biology, Holland Laboratory, American Red Cross, Rockville, Maryland 20855, USA
    J Clin Invest 112:1533-40. 2003
    ....
  41. pmc Serpins in thrombosis, hemostasis and fibrinolysis
    J C Rau
    Department of Pathology and Laboratory Medicine, Carolina Cardiovascular Biology Center, School of Medicine, University of North Carolina, Chapel Hill, NC 27599 7035, USA
    J Thromb Haemost 5:102-15. 2007
    ..in these processes are regulated by feedback loops, local cofactor molecules, and serine protease inhibitors (serpins)...
  42. ncbi Two functional epitopes of pigment epithelial-derived factor block angiogenesis and induce differentiation in prostate cancer
    Stephanie Filleur
    Department of Urology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois 60611, USA
    Cancer Res 65:5144-52. 2005
    ..Our results map active regions for the two PEDF functions, signaling via distinct receptors, identify candidate peptides, and provide their mechanism of action for future development of PEDF-based tumor therapies...
  43. ncbi Focus on Molecules: Pigment epithelium-derived factor (PEDF)
    S Patricia Becerra
    NIH NEI, 7 Memorial Drive, Room 304, Building 7, Bethesda, MD 20892, USA
    Exp Eye Res 82:739-40. 2006
  44. ncbi Nuclear cytokine-activated IKKalpha controls prostate cancer metastasis by repressing Maspin
    Jun Li Luo
    Laboratory of Gene Regulation and Signal Transduction, Department of Pharmacology and Cancer Center, School of Medicine, University of California, San Diego, 9500 Gilman Drive, La Jolla, California 92093 0723, USA
    Nature 446:690-4. 2007
    ..We propose that tumour-infiltrating RANKL-expressing cells lead to nuclear IKKalpha activation and inhibition of Maspin transcription, thereby promoting the metastatic phenotype...
  45. pmc Serpins flex their muscle: I. Putting the clamps on proteolysis in diverse biological systems
    Gary A Silverman
    Department of Pediatrics and Cell Biology and Physiology, Children s Hospital of Pittsburgh and Magee Womens Hospital, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15201, USA
    J Biol Chem 285:24299-305. 2010
    b>Serpins compose the largest superfamily of peptidase inhibitors and are well known as regulators of hemostasis and thrombolysis...
  46. ncbi Serum vaspin concentrations are closely related to insulin resistance, and rs77060950 at SERPINA12 genetically defines distinct group with higher serum levels in Japanese population
    Sanae Teshigawara
    Department of Medicine and Clinical Science, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, 2 5 1 Shikata cho, Kita ku, Okayama 700 8558, Japan
    J Clin Endocrinol Metab 97:E1202-7. 2012
    ..Vaspin is an adipokine with insulin-sensitizing effects identified from visceral adipose tissues of genetically obese rats...
  47. ncbi Vaspin prevents TNF-α-induced intracellular adhesion molecule-1 via inhibiting reactive oxygen species-dependent NF-κB and PKCθ activation in cultured rat vascular smooth muscle cells
    Sukanya Phalitakul
    Laboratory of Veterinary Pharmacology, School of Veterinary Medicine, Kitasato University, Aomori 034 8628, Japan
    Pharmacol Res 64:493-500. 2011
    ..Consequently, vaspin could play inhibitory roles on inflammatory states of vascular SMCs...
  48. ncbi Metformin decreases the adipokine vaspin in overweight women with polycystic ovary syndrome concomitant with improvement in insulin sensitivity and a decrease in insulin resistance
    Bee K Tan
    Endocrinology and Metabolism Group, Clinical Sciences Research Institute, Warwick Medical School, University of Warwick, Coventry, UK
    Diabetes 57:1501-7. 2008
    ..Ex vivo regulation of adipose tissue vaspin and the effects of metformin treatment on circulating vaspin levels in PCOS subjects were also studied...
  49. ncbi Human clade B serpins (ov-serpins) belong to a cohort of evolutionarily dispersed intracellular proteinase inhibitor clades that protect cells from promiscuous proteolysis
    G A Silverman
    Division of Newborn Medicine, Children s Hospital, Dept of Pediatrics, Harvard Medical School, 300 Longwood Ave, Enders 970, Boston, Massachusetts 02115, USA
    Cell Mol Life Sci 61:301-25. 2004
    b>Serpins are unique among the various types of active site proteinase inhibitors because they covalently trap their targets by undergoing an irreversible conformational rearrangement...
  50. ncbi Antiangiogenic property of pigment epithelium-derived factor in hepatocellular carcinoma
    Kojiro Matsumoto
    First Department of Internal Medicine, Nagasaki University School of Medicine, Sakamoto, Japan
    Hepatology 40:252-9. 2004
    ..Reduction of serum PEDF concentration associated with the development of chronic liver diseases may contribute to the progression of HCC. In addition, gene therapy using PEDF may provide an efficient treatment for HCC...
  51. ncbi Pigment epithelium-derived factor is a substrate for matrix metalloproteinase type 2 and type 9: implications for downregulation in hypoxia
    Luigi Notari
    Laboratory of Retinal Cell and Molecular Biology, National Eye Institute, National Institutes of Health, Bethesda, MD 20892 0607, USA
    Invest Ophthalmol Vis Sci 46:2736-47. 2005
    ..Because hypoxia and VEGF regulate matrix metalloproteinases (MMPs), their effects on PEDF proteolysis were explored...
  52. ncbi Pigment epithelium-derived factor gene therapy inhibits human pancreatic cancer in mice
    Ryunosuke Hase
    Department of Surgical Oncology, Division of Cancer Medicine, Hokkaido University Graduate School of Medicine, Sapporo, Hokkaido, Japan
    Clin Cancer Res 11:8737-44. 2005
    ..The purpose of this study was to investigate whether PEDF gene is a potent tumor suppressor and a potential candidate for cancer gene therapy...
  53. ncbi Pigment epithelium-derived factor downregulates vascular endothelial growth factor (VEGF) expression and inhibits VEGF-VEGF receptor 2 binding in diabetic retinopathy
    Sarah X Zhang
    Department of Medicine, Department of Cell Biology, University of Oklahoma Health Sciences Center, 941 Stanton L Young Blvd, Oklahoma City, OK, USA
    J Mol Endocrinol 37:1-12. 2006
    ..The decrease in PEDF levels in the retina is at least partially responsible for the increase in VEGF expression and subsequent vascular leakage and neovascularization in diabetes...
  54. pmc A therapeutic strategy for choroidal neovascularization based on recruitment of mesenchymal stem cells to the sites of lesions
    Hui Yuan Hou
    Department of Ophthalmology, Eye Institute of Chinese PLA, Xijing Hospital, Fourth Military Medical University, Xi an, China
    Mol Ther 18:1837-45. 2010
    ..These results suggest that MSCs contribute to CNV and could serve as delivery vehicles of antiangiogenic agents for the treatment of a range of CNV-associated diseases...
  55. ncbi Pigment epithelium-derived factor protects cultured retinal pericytes from advanced glycation end product-induced injury through its antioxidative properties
    Sho ichi Yamagishi
    Division of Endocrinology and Metabolism, Department of Medicine, Kurume University School of Medicine, Kurume 830 0011, Japan
    Biochem Biophys Res Commun 296:877-82. 2002
    ..Our present study suggests that substitution of PEDF proteins may be a promising strategy in treatment of patients with early diabetic retinopathy...
  56. ncbi Pigment epithelium-derived factor behaves like a noninhibitory serpin. Neurotrophic activity does not require the serpin reactive loop
    S P Becerra
    Laboratory of Retinal Cell and Molecular Biology, National Eye Institute, National Institutes of Health, Bethesda, Maryland 20892, USA
    J Biol Chem 270:25992-9. 1995
    ..Altogether our data indicate that PEDF belongs to the subgroup of noninhibitory serpins and that its N-terminal region confers a neurite-promoting activity to the protein...
  57. ncbi Biological functions of maspin
    Caleb M Bailey
    Department of Anatomy and Cell Biology, The Carver College of Medicine, University of Iowa, Iowa City, IA, USA
    J Cell Physiol 209:617-24. 2006
    ....
  58. ncbi Overexpression of squamous cell carcinoma antigen in idiopathic pulmonary fibrosis: clinicopathological correlations
    F Calabrese
    Department of Diagnostic Medical Sciences and Special Therapies, University of Padua Medical School, Via Gabelli, 61 Padua, Italy
    Thorax 63:795-802. 2008
    ..At present, no information is available on its expression in IPF...
  59. ncbi The effect of weight loss and treatment with metformin on serum vaspin levels in women with polycystic ovary syndrome
    Ekaterini Koiou
    Division of Endocrinology and Human Reproduction, Second Department of Obstetrics and Gynecology, Aristotle University of Thessaloniki, Hippokration Hospital, Thessaloniki, Greece
    Endocr J 58:237-46. 2011
    ..001) and with waist circumference in controls (p=0.015). In conclusion, serum vaspin levels are elevated in PCOS but neither a small weight loss nor metformin affect vaspin levels significantly...
  60. pmc Molecular ordering of the Fas-apoptotic pathway: the Fas/APO-1 protease Mch5 is a CrmA-inhibitable protease that activates multiple Ced-3/ICE-like cysteine proteases
    S M Srinivasula
    Department of Biochemistry and Molecular Pharmacology, Jefferson Medical College, Philadelphia, PA 19107, USA
    Proc Natl Acad Sci U S A 93:14486-91. 1996
    ..On the other hand, Mch4 could be a second upstream protease that is responsible for activation of the same protease cascade in CrmA-insensitive apoptotic pathways...
  61. ncbi Vaspin (SERPINA12) genotypes and risk of type 2 diabetes: Results from the MONICA/KORA studies
    K Kempf
    Institute for Clinical Diabetes Research, German Diabetes Centre, Leibniz Institute for Diabetes Research at Heinrich Heine University Dusseldorf, Germany
    Exp Clin Endocrinol Diabetes 118:184-9. 2010
    ..35 [1.59; 3.46] versus AT/TT). This association appears to be independent of obesity. Our finding corroborates previous studies that suggested a link between the novel adipokine vaspin and glucose metabolism...
  62. pmc The ovalbumin serpins revisited: perspective from the chicken genome of clade B serpin evolution in vertebrates
    Charaf Benarafa
    CBR Institute for Biomedical Research and Department of Pediatrics, Harvard Medical School, Boston, MA 02115, USA
    Proc Natl Acad Sci U S A 102:11367-72. 2005
    ..Although serpins have been identified in isolated members of archea, bacteria, and plants, a remarkable expansion is found in ..
  63. pmc Alpha1-antitrypsin polymerization and the serpinopathies: pathobiology and prospects for therapy
    David A Lomas
    Respiratory Medicine Unit, Department of Medicine, University of Cambridge, Cambridge Institute for Medical Research, Cambridge, United Kingdom
    J Clin Invest 110:1585-90. 2002
  64. ncbi Overexpression of SERPIN B3 promotes epithelial proliferation and lung fibrosis in mice
    Francesca Lunardi
    Department of Diagnostic Medical Sciences and Special Therapies, University of Padua, Padua, Italy
    Lab Invest 91:945-54. 2011
    ..This study provides in vivo evidence for a role of SERPIN B3 in inhibiting inflammation and favoring epithelial proliferation with increased TGF-β secretion and thus the likelihood of consequent fibrogenesis...
  65. ncbi Endogenous inhibition of histone deacetylase 1 by tumor-suppressive maspin
    Xiaohua Li
    Department of Pathology, School of Medicine, Wayne State University, Detroit, MI 48201, USA
    Cancer Res 66:9323-9. 2006
    ....
  66. pmc Nuclear, compared with combined nuclear and cytoplasmic expression of maspin, is linked in lung adenocarcinoma to reduced VEGF-A levels and in Stage I, improved survival
    Amy Frey
    Department of Pathology, Harper University Hospital, Wayne State University, Detroit, MI 48201, USA
    Histopathology 54:590-7. 2009
    ....
  67. ncbi Vaspin and its correlation with insulin sensitivity indices in obese children
    Selami Suleymanoglu
    Department of Pediatrics, GATA Medical Faculty, Istanbul, Turkey
    Diabetes Res Clin Pract 84:325-8. 2009
    ..The aim of this study was to assess the vaspin and adiponectin concentrations on markers of insulin sensitivity and obesity in pubertal obese children and adolescents...
  68. ncbi Vascular niche factor PEDF modulates Notch-dependent stemness in the adult subependymal zone
    Celia Andreu-Agullo
    Departamento de Biología Celular and CIBER en Enfermedades Neurodegenerativas, Universidad de Valencia, Burjassot, Spain
    Nat Neurosci 12:1514-23. 2009
    ..Our data provide a basis for stemness regulation in vascular niches and indicate that Notch and PEDF cooperate to regulate self-renewal...
  69. ncbi Role of squamous cell carcinoma antigen-1 on liver cells after partial hepatectomy in transgenic mice
    Gianmarco Villano
    Department of Clinical and Experimental Medicine, University of Padova, I 35123 Padova, Italy
    Int J Mol Med 25:137-43. 2010
    ..In conclusion, transgenic mice expressing SCCA1 showed higher liver regenerative potential compared to wild-type mice, supporting the dual role of this serpin as an anti-apoptotic and pro-proliferative stimulus for liver cells in vivo...
  70. ncbi SERPINB12 is a novel member of the human ov-serpin family that is widely expressed and inhibits trypsin-like serine proteinases
    Y S Askew
    Department of Pediatrics, Harvard Medical School, Children s Hospital, Boston, Massachusetts 02115, USA
    J Biol Chem 276:49320-30. 2001
    ..Most serpins are secreted and attain physiologic concentrations in the blood and extracellular fluids...
  71. pmc Depletion of endogenous kallistatin exacerbates renal and cardiovascular oxidative stress, inflammation, and organ remodeling
    Yuying Liu
    Department of Biochemistry and Molecular Biology, Medical University of South Carolina, 173 Ashley Ave, Charleston, SC 29425 2211, USA
    Am J Physiol Renal Physiol 303:F1230-8. 2012
    ..Taken together, these results implicate an important role for endogenous KS in protection against salt-induced renal and cardiovascular injury in rats by suppressing oxidative stress, inflammation, hypertrophy, and fibrosis...
  72. ncbi Maspin: molecular mechanisms and therapeutic implications
    Thomas M Bodenstine
    Children s Hospital of Chicago Research Center, Robert H Lurie Comprehensive Cancer Center, Northwestern University Feinberg School of Medicine, 225 E Chicago Avenue, Box 222, Chicago, IL 60611, USA
    Cancer Metastasis Rev 31:529-51. 2012
    ..We provide insight into the immense therapeutic potential of Maspin and the challenges related to its successful clinical translation...
  73. ncbi Maspin polymorphism associated with apoptosis susceptibility and in vivo tumorigenesis
    Hye Lim Jang
    Cancer Center, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 135 710, Korea
    Int J Mol Med 22:333-8. 2008
    ..Therefore, P176S (C526T) substitution of maspin may result in a partial loss of the tumor suppressor function of this protein, contributing to decreased susceptibility to apoptosis and malignant progression...
  74. pmc Blocking the Wnt pathway, a unifying mechanism for an angiogenic inhibitor in the serine proteinase inhibitor family
    Bin Zhang
    Department of Cell Biology, College of Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA
    Proc Natl Acad Sci U S A 107:6900-5. 2010
    ..These results suggest that SERPINA3K is a high-affinity, endogenous antagonist of LRP6. The blockade of Wnt signaling may represent a unifying mechanism for the anti-inflammatory and anti-angiogenic effects of SERPINA3K...
  75. pmc Protective effect of perindopril on diabetic retinopathy is associated with decreased vascular endothelial growth factor-to-pigment epithelium-derived factor ratio: involvement of a mitochondria-reactive oxygen species pathway
    Zhi Zheng
    Department of Ophthalmology, First People s Hospital of Shanghai, Shanghai Jiaotong University, Shanghai, China
    Diabetes 58:954-64. 2009
    ....
  76. ncbi Manduca sexta serpin-3 regulates prophenoloxidase activation in response to infection by inhibiting prophenoloxidase-activating proteinases
    Yifei Zhu
    Department of Biochemistry, Kansas State University, Manhattan, KS 66506, USA
    J Biol Chem 278:46556-64. 2003
    ..Kinetic analysis of PAP-serpin-3 association strongly suggests that serpin-3 is a physiological regulator of the pro-PO activation reaction...
  77. ncbi Adenoviral vector-delivered pigment epithelium-derived factor for neovascular age-related macular degeneration: results of a phase I clinical trial
    Peter A Campochiaro
    Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA
    Hum Gene Ther 17:167-76. 2006
    ..11 in patients with neovascular AMD should be performed...
  78. ncbi A novel adipocytokine, vaspin inhibits platelet-derived growth factor-BB-induced migration of vascular smooth muscle cells
    Sukanya Phalitakul
    Laboratory of Veterinary Pharmacology, School of Veterinary Medicine, Kitasato University, Aomori 034 8628, Japan
    Biochem Biophys Res Commun 423:844-9. 2012
    ..The present study for the first time revealed that vaspin inhibits PDGF-BB-induced SMCs migration through inhibiting p38/HSP27 signals via preventing the ROS generation...
  79. pmc Matriptase-3 is a novel phylogenetically preserved membrane-anchored serine protease with broad serpin reactivity
    Roman Szabo
    Proteases and Tissue Remodeling Unit, Oral and Pharyngeal Cancer Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, 30 Convent Drive, Bethesda, MD 20892, USA
    Biochem J 390:231-42. 2005
    ..Interestingly, activated matriptase-3 formed stable inhibitor complexes with an array of serpins, including plasminogen activator inhibitor-1, protein C inhibitor, alpha1-proteinase inhibitor, alpha2-..
  80. pmc Nuclear and cytoplasmic Maspin expression in primary non-small cell lung cancer
    Matthias Woenckhaus
    Institute of Pathology, University of Regensburg, Regensburg, Germany
    J Clin Pathol 60:483-6. 2007
    ..To investigate whether nuclear and cytoplasmic Maspin expression is associated with distinct clinicopathological parameters and TP53 expression in a representative series of primary non-small cell lung cancer (NSCLC)...
  81. ncbi Maspin expression in invasive breast cancer: association with other prognostic factors
    Syed K Mohsin
    Breast Center, Baylor College of Medicine, Houston, Texas 77030, USA
    J Pathol 199:432-5. 2003
    ..Additional studies are needed to evaluate further this expression profile of maspin in breast cancer...
  82. ncbi Pigment epithelium-derived factor (PEDF) is one of the most abundant proteins secreted by human adipocytes and induces insulin resistance and inflammatory signaling in muscle and fat cells
    S Famulla
    Institute of Clinical Biochemistry and Pathobiochemistry, German Diabetes Center, Dusseldorf, Germany
    Int J Obes (Lond) 35:762-72. 2011
    ..The aim of this study was to investigate the regulation and autocrine function of PEDF in human adipocytes and to determine its paracrine effects on human skeletal muscle cells (hSkMC) and human smooth muscle cells (hSMC)...
  83. ncbi Cross-class inhibition of the cysteine proteinases cathepsins K, L, and S by the serpin squamous cell carcinoma antigen 1: a kinetic analysis
    C Schick
    Department of Pediatrics, The Harvard Medical School, Children s Hospital, 300 Longwood Avenue, Boston, Massachusetts 02115, USA
    Biochemistry 37:5258-66. 1998
    ..SCCA) 1 and 2 are tandemly arrayed genes that encode two high-molecular-weight serine proteinase inhibitors (serpins)...
  84. ncbi Serum vaspin concentrations in relation to insulin sensitivity following RYGB-induced weight loss
    Ammon Handisurya
    Department of Internal Medicine III, Division of Endocrinology and Metabolism, Medical University of Vienna, Waehringer Guertel 18 20, 1090 Vienna, Austria
    Obes Surg 20:198-203. 2010
    ..Our objective was to evaluate the impact of acute weight loss and metabolic changes on serum vaspin concentrations in morbidly obese subjects following laparoscopic Roux-en-Y gastric bypass (RYGB) surgery...
  85. ncbi Vaspin is related to gender, puberty and deteriorating insulin sensitivity in children
    A Korner
    Department of Women and Child Health, University Hospital for Children and Adolescents, University of Leipzig, Leipzig, Germany
    Int J Obes (Lond) 35:578-86. 2011
    ..Visceral adipose tissue-derived serine protease inhibitor (vaspin) has been suggested as a novel adipocytokine related to obesity and insulin sensitivity in adults...
  86. pmc The roles of serpins in mosquito immunology and physiology
    Melissa M Gulley
    Kansas State University, Division of Biology, Manhattan, KS 66506, USA
    J Insect Physiol 59:138-47. 2013
    ..b>Serpins have been shown in many animals to be key regulators of innate immune reactions...
  87. ncbi Pleiotrophic inhibition of pericellular urokinase-type plasminogen activator system by endogenous tumor suppressive maspin
    H Biliran
    Department of Pathology, Wayne State University School of Medicine, Detroit, Michigan 48201, USA
    Cancer Res 61:8676-82. 2001
    ..Furthermore, our results support a current hypothesis that maspin blocks tumor invasion and motility by inhibiting localized pericellular proteolysis...
  88. ncbi Tick-Encoded serine proteinase inhibitors (serpins); potential target antigens for tick vaccine development
    A Muleng
    Graduate School of Veterinary Medicine, Hokkaido University, Sapporo, Japan
    J Vet Med Sci 63:1063-9. 2001
    ....
  89. ncbi SERPINB3 modulates TGF-beta expression in chronic liver disease
    Cristian Turato
    I O V IRCCS, Padua, Italy
    Lab Invest 90:1016-23. 2010
    ..In conclusion, chronically damaged hepatocytes produce SERPINB3 and TGF-beta, and the anti-protease activity of this serpin might be implicated in TGF-beta1 induction...
  90. ncbi Over-expression of SERPINB3 in hepatoblastoma: a possible insight into the genesis of this tumour?
    Cristian Turato
    Istituto Oncologico Veneto IOV IRCCS, Padua, Italy
    Eur J Cancer 48:1219-26. 2012
    ....
  91. ncbi PEDF: a potential molecular therapeutic target with multiple anti-cancer activities
    Eugene T H Ek
    Department of Orthopaedics, University of Melbourne St Vincent s Hospital, Melbourne, PO Box 2900, Fitzroy, Melbourne, Australia
    Trends Mol Med 12:497-502. 2006
    ..We also discuss the prospects for PEDF therapy and the need for a closer evaluation of issues such as delivery, stability and potential toxicity...
  92. ncbi Pigment epithelium-derived factor inhibits advanced glycation end-products-induced cytotoxicity in retinal pericytes
    S Sheikpranbabu
    Department of Biotechnology, Division of Molecular and Cellular Biology, Kalasalingam University Kalasalingam Academy of Research and Education, Krishnankoil 626126, Anand Nagar, Tamilnadu, India
    Diabetes Metab 37:505-11. 2011
    ..This study investigated the effects of pigment epithelium-derived factor (PEDF) on advanced glycation end-product (AGE)-induced cytotoxicity in porcine retinal pericytes and the signalling mechanism involved...
  93. ncbi Serine proteinase inhibitors in arthropod immunity
    M R Kanost
    Department of Biochemistry, Kansas State University, Manhattan 66506, USA
    Dev Comp Immunol 23:291-301. 1999
    ..Some may inhibit fungal or bacterial proteinases. Others probably have roles in regulating endogenous proteinases involved in coagulation, prophenol oxidase activation, or cytokine activation...
  94. ncbi Aberrant expression of serpin squamous cell carcinoma antigen 2 in human tumor tissues and cell lines: evidence of protection from tumor necrosis factor-mediated apoptosis
    Atsushi Takeda
    Laboratory of Biochemistry, Faculty of Arts and Sciences, Sagami Women s University, Sagamihara shi, Kanagawa, Japan
    Biol Chem 383:1231-6. 2002
    ..Thus, SCCA2 overexpression in squamous tumor cells contributed to their survival by protecting them against TNF-alpha-induced apoptosis...
  95. ncbi Conformational properties of serine proteinase inhibitors (serpins) confer multiple pathophysiological roles
    S Janciauskiene
    Department of Medicine, Wallenberg Laboratory, Ing 46, Malmo University Hospital, S 20502, Malmo, Sweden
    Biochim Biophys Acta 1535:221-35. 2001
    Serine proteinase inhibitors (Serpins) are irreversible suicide inhibitors of proteases that regulate diverse physiological processes such as coagulation, fibrinolysis, complement activation, angiogenesis, apoptosis, inflammation, ..
  96. ncbi Anti-chondrosarcoma effects of PEDF mediated via molecules important to apoptosis, cell cycling, adhesion and invasion
    Mei Lin Tan
    Department of Orthopaedics, St Vincent s Hospital Melbourne, Vic, Australia
    Biochem Biophys Res Commun 398:613-8. 2010
    ..These findings seminally indicate that PEDF may have potential as an anti-cancer agent against chondrosarcoma...
  97. ncbi Viral inhibition of inflammation: cowpox virus encodes an inhibitor of the interleukin-1 beta converting enzyme
    C A Ray
    Department of Microbiology and Immunology, Duke University Medical Center, Durham, North Carolina 27710
    Cell 69:597-604. 1992
    ..These viral countermeasures to host defenses against infection may contribute significantly to the pathology associated with poxvirus infections...
  98. ncbi Association of maspin expression with the malignancy grade and tumor vascularization in breast cancer tissues
    T Hojo
    Growth Factor Division, National Cancer Center Research Institute, 5-1-1 Tsukiji, Chuo-ku, 104-0045, Tokyo, Japan
    Cancer Lett 171:103-10. 2001
    ..These results suggest that maspin production in myoepithelial cells could downregulate the malignant phenotype of breast cancer...
  99. pmc Three pairs of protease-serpin complexes cooperatively regulate the insect innate immune responses
    Rui Jiang
    National Research Laboratory of Defense Proteins, College of Pharmacy, Pusan National University, Busan 609 735, Korea
    J Biol Chem 284:35652-8. 2009
    b>Serpins are known to be necessary for the regulation of several serine protease cascades...
  100. pmc Polarized secretion of PEDF from human embryonic stem cell-derived RPE promotes retinal progenitor cell survival
    DanHong Zhu
    Department of Pathology, Keck School of Medicine, University of Southern California, Los Angeles, California 90089, USA
    Invest Ophthalmol Vis Sci 52:1573-85. 2011
    ..The purpose of this study was to determine the effect of polarization of hES-RPE monolayers on their ability to promote survival of RPCs...
  101. ncbi Pigment epithelium-derived factor gene therapy targeting retinal ganglion cell injuries: neuroprotection against loss of function in two animal models
    Masanori Miyazaki
    Department of Ophthalmology, Graduate School of Medical Sciences, Kyushu University, Higashi ku, Fukuoka, Japan
    Hum Gene Ther 22:559-65. 2011
    ..These findings show that neuroprotective gene therapy using hPEDF can protect against retinal ganglion cell death, and support the potential feasibility of neuroprotective therapy for intractable glaucoma...

Research Grants64

  1. Serpin Modulation of Inflammatory Vasculitis; Potential for Immunomodulatory Ther
    ALEXANDRA ROSE LUCAS; Fiscal Year: 2010
    ..Two innovative therapeutic approaches, based upon the infusion of serpins, one derived from a myxoma virus, Serp-1, and one mammalian serpin, neuroserpin (NSP), have been investigated in ..
  2. Intracellular Serpin Regulation of Intestinal Cell Necrosis
    GARY ARTHUR SILVERMAN; Fiscal Year: 2012
    ..Extensive searches within the largest family of peptidase inhibitors, the serpins (e.g., antithrombin and [unreadable]1-antitrypsin), failed to yield candidate regulatory genes...
  3. Tick feeding regulation by orthologous tick saliva serine protease inhibitors
    Albert Mulenga; Fiscal Year: 2013
    ..and validation of Amblyomma americanum and Ixodes scapularis tick saliva serine protease inhibitors (serpins) as vaccine target antigens for immunization of white tailed deer against tick infestation...
  4. Plasminogen activator inhibitor-1 in tumor progression and metastasis
    Yves A DeClerck; Fiscal Year: 2013
    ..Plasminogen activator inhibitor-1 (PAI-1) is a member of the family of endogenous serine protease inhibitors (serpins) that controls the activation of plasminogen into plasmin by tissue and urokinase type plasminogen activators (..
  5. Novel Protective Antiapoptotic Action of Alpha 1-Antitrypsin In Emphysema
    Rubin M Tuder; Fiscal Year: 2011
    ..antitrypsin (A1AT) deficiency emphasizes the role of A1AT as an elastase inhibitor, serine protease inhibitors (Serpins), including A1 AT, have broader biological effects beyond their classical action as protease inhibitors...
  6. Physiology and Molecular Biology of Factor XI
    David Gailani; Fiscal Year: 2013
    ..fXI, potentiating its activation by thrombin, fXII and autoactivation, and may down-regulate fXIa inhibition by serpins. In Aim 1, we will use an ex vivo flow model to study the importance of fXI and fXII to thrombus formation in ..
  7. MOLECULAR BASIS OF BLOOD COAGULATION REGULATION
    Steven T Olson; Fiscal Year: 2013
    ..Two serpins, anti-thrombin and protein Z-dependent protease inhibitor (ZPI), are known to inhibit procoagulant proteases in a ..
  8. Serpin Regulation of Coagulation Proteases
    Alireza R Rezaie; Fiscal Year: 2013
    ..by applicant): The proteolytic activity of coagulation proteases is regulated by the serine protease inhibitors (serpins) in plasma...
  9. PROTEINASE SYSTEMS IN INSECT HEMOLYMPH
    Michael R Kanost; Fiscal Year: 2013
    ..3. Investigate the regulation of protease pathways in hemolymph by serpins, using in vitro, ex vivo, and in vivo experimental approaches...
  10. Serine Proteinase Inhibitors (Serpins) in Tick Feeding and Physiology
    Albert Mulenga; Fiscal Year: 2009
    ..In humans, serpins are involved in regulation of important of proteolytic pathways that are essential to life such as blood ..
  11. Post-Reductionist Protein Folding: Determining the In-cell Folding Energy Landsca
    Daniel N Hebert; Fiscal Year: 2013
    ..We will focus on an important family of secreted proteins, the inhibitory serpins, which fold into native structures with high contact order...
  12. The Molecular Basis of Serpin Function and Disfunction
    Patrick L Wintrode; Fiscal Year: 2011
    ..b>Serpins are involved in the regulation of many physiological processes including fibrinolysis, complement activation, ..
  13. Neuroprotection with serpins during cardiac surgery
    Richard A Jonas; Fiscal Year: 2010
    ..Furthermore recent reports in the neuroscience literature applying cell culture models suggest that some serpins may be neuroprotective through inhibition of excitotoxicity...
  14. CTL EFFECTOR MECHANISMS IN ADENOVIRAL HEPATITIS
    DWAIN LOUIS THIELE; Fiscal Year: 2010
    ..In proposed studies, we will determine the repertoire of serine proteinase inhibitors (serpins) expressed in normal and virally infected murine hepatocytes and determine the role of cytokines in regulating ..
  15. Glutathione S-Transferases in Drug and Stress Response
    Kenneth D Tew; Fiscal Year: 2013
    ..myeloproliferative drugs) may impart proliferative effects through S-glutathionylation of the protease inhibitor serpins. Mechanistically, these protein families are subject to redox regulation and have roles in regulation of marrow ..
  16. Enzymatic Regulation of the Podocyte
    Jochen Reiser; Fiscal Year: 2013
    ..We will utilize this mouse and study inhibition of cCatL by a group of enzymes called serpins. Our initial focus will be on SERPINB13 (hurpin) which is classically located in the cytosol of skin cels and ..
  17. Role of gammaHV68 M1 antigen in Vbeta4+ T cell expansion and fibrosis
    Samuel H Speck; Fiscal Year: 2012
    ..The M1 antigen, which bears sequence homology to some pox virus serpins (although it lacks critical catalytic residues) and to the ?HV68 secreted high affinity chemokine binding protein ..
  18. Engineering a chimeric serpin as a preventive therapeutic for ischemic stroke
    JILL C RAU; Fiscal Year: 2010
    ..Serine protease inhibitors (serpins) are a family of proteins with high structural homology...
  19. Laser microdissection for molecular analysis of oral, dental and craniofacial dis
    Xiaofeng Zhou; Fiscal Year: 2010
    ..in periodontal development and the periodontal ligament, 6) epithelial-connective tissue interactions and scar formation, 7) molecular mechanisms of serpins in oral cancer tumorgenesis, 8) molecular analysis of rhabdomyosarcoma.
  20. Characterization of the An. gambiae LL3/SRPN6 pathway in response to Plasmodium i
    RYAN CHAD SMITH; Fiscal Year: 2012
    ..b>Serpins are conserved components of many organisms and have been implicated in a variety of cellular events including the ..
  21. Alternaria proteases and protease defenses in asthma
    Michael O Daines; Fiscal Year: 2010
    ..There are endogenous inhibitors of proteases, including SERine Protease INhibitors (Serpins) and Stefin protease inhibitors, which are differentially upregulated with Alternaria exposure...
  22. Alternaria proteases and protease defenses in asthma
    Michael O Daines; Fiscal Year: 2013
    ..There are endogenous inhibitors of proteases, including SERine Protease INhibitors (Serpins) and Stefin protease inhibitors. These inhibitors are strongly upregulated with Alternaria exposure...
  23. The Role of Intracellular Serpins in the Regulation of Necrosis
    Mark T Miedel; Fiscal Year: 2012
    ..Ultimately, these studies will provide the basis for development of highly specific treatments for patients with necrosis-associated disorders. ..
  24. A Robust Predictive Method for Heparin and Heparan Sulfate Binding to Proteins
    UMESH RAMANLAL DESAI; Fiscal Year: 2010
    ..The working hypothesis in this aim is that application of CVLS to i) serpins (antithrombin and heparin cofactor II);ii) proteases (factors IIa, Xa and IXa of the coagulation cascade);and iii)..
  25. GENE REGULATION OF MAMMALIAN DNA VIRUSES
    Richard Moyer; Fiscal Year: 2005
    ..They focus here on poxvirus-encoded proteinase inhibitors (serpins). Orthopoxviruses, including cowpox virus (CPV), encode three serpins: SPI-1, SPI-2/crmA and SPI-3...
  26. Mechanisms of Hemostatic Protease Inhibition by Serpins
    Ingrid M Verhamme; Fiscal Year: 2010
    The long-term goal is to define the molecular mechanisms of thrombin (T) inhibition by the serpins, heparin cofactor II (HCII) and plasminogen activator inhibitor-1 (PAI-1), implicated in arterial thrombosis...
  27. Poxvirus proteins involved in virion binding, membrane fusion, & entry into cells
    Richard Moyer; Fiscal Year: 2007
    ..We focus here on poxvirus- encoded serine proteinase inhibitors (serpins). Orthopoxviruses, including cowpox virus (CPV), encode three serpins: SPI-1, SPl-2/crmA and SPI-3...
  28. MOLECULAR MECHANISM OF THROMBIN INHIBITION
    Scott Cooper; Fiscal Year: 2003
    ..The objective of this research is to better understand the different mechanisms by which the serpins antithrombin (AT) and protein C inhibitor (PCI) inhibit free thrombin and thrombin bound to thrombomodulin (TM)...
  29. SERINE PROTEINASE INHIBITORS IN INSECTS
    Michael Kanost; Fiscal Year: 1993
    Human plasma contains a superfamily of serine proteinase inhibitors, the serpins, which are glycoproteins of Mr = 40,000- 60,000...
  30. REGULATION OF EXTRACELLULAR PROTEOLYSIS BY SERPINS
    DANIEL KNAUER; Fiscal Year: 2004
    ..This places PN1, FXIa, APP and the LRP in a common biochemical pathway that may be directly involved in Alzheimer's disease pathology. ..
  31. RECOMBINANT SERPINS AND NEUTROPHILS IN ACUTE LUNG INJURY
    Michael Plotnick; Fiscal Year: 2000
    ..to our understanding of the biochemical properties and biological functions of serine protease inhibitor (serpins) as well as provide me with a foundation for a career as an independent investigator in the molecular and ..
  32. CELLULAR INTERACTIONS OF PLASMA PROTEINS
    Peter Walsh; Fiscal Year: 2001
    ..Project 3 (S.C. bock, Serpin Structure and the Development of Neutrophil-Resistant Serpins) will focus on the structure-activity relationships with a naturally occurring anticoagulant serpin, antithrombin ..
  33. SERINE PROTEASE INHIBITORS & MECHANISMS OF INFLAMATION
    Harvey Rubin; Fiscal Year: 2004
    ..We are studying a family of high molecular weight plasma and cellular proteins, the serpins--serine protease inhibitors, some of which have evolved the remarkable property of inhibiting these proteases ..
  34. Tyrosine Sulfation and Chemokine Receptor Function
    Kevin Moore; Fiscal Year: 2006
    ..of proteins are known to be tyrosine sulfated in man, including certain adhesion molecules, coagulation factors, serpins, extracellular matrix proteins, and hormones and some of these require sulfation for optimal function...
  35. Anti-inflammatory Serpin(AAT and Elafin) Gene Transfers*
    Sihong Song; Fiscal Year: 2003
    ..Lines of evidence suggest that serpins, namely AAT and elafin, may play important roles in protecting islets from autoimmunity and alloimmnunity...
  36. ANALYSIS OF THE AIRWAY ANTIPROTEINASE DEFENSE SYSTEM
    Sule Cataltepe; Fiscal Year: 2006
    ..and distribution patterns of SCCA1 and SCCA2 in the airways, the investigators hypothesize that these two serpins protect the airways against proteinase mediated injury...
  37. Analysis of Airway Serpins in Baboon Models of BPD
    Sule Cataltepe; Fiscal Year: 2005
    ..Among the local proteinase inhibitors, members of the ov-serpin family (ovalbumin-related serpins) are an emerging group of proteins that are abundantly expressed by several cell types in the lung, including ..
  38. SERPIN INTERACTION WITH SERINE PROTEINASES
    BARRY COOPERMAN; Fiscal Year: 2006
    DESCRIPTION (provided by applicant): Serine proteinase inhibitors (serpins) play a central role in a wide variety of physiologic processes involved in aging...
  39. High Flux X-ray Crystallography Data Collection System
    Harlan Wright; Fiscal Year: 2004
    ..agents and cardiovascular treatment; development of anti-sickling agents for sickle cell hemoglobin; serpins and their complexes with heparin and other ligands, which play critical roles in fibrinolysis, thrombosis and ..
  40. HEPARIN ACTIVATION OF ANTITHROMBIN III
    Susan Bock; Fiscal Year: 1999
    ..of this information and knowledge of protein conformational changes that occur during proteinase inhibition by serpins, a working model for the molecular mechanism underlying ATIII heparin cofactor activity has been proposed...
  41. TYROSYLPROTEIN SULFOTRANSFERASES
    Kevin Moore; Fiscal Year: 2002
    ..biology contain tyrosine sulfate, including adhesion molecules, coagulation factors, complement components, serpins, and extracellular matrix proteins...
  42. SERPIN STRUCTURE AND FUNCTION
    PETER GETTINS; Fiscal Year: 2004
    ..those on the structure of the nature of the inhibition mechanism of both serine and cysteine proteinases and how serpins are able to kinetically trap complexes with proteinase (Project 2, Steven Olson, P.I...
  43. Reverse genetics of mosquito systemic immunity
    Alexander Raikhel; Fiscal Year: 2009
    ..for the production of regulatory molecules, such as cytokines, serine pro-proteases and their inhibitors (serpins). Stable, dominant-negative and bloodmeal-activated, over-expressed Dorsal Aedes strains will be generated...
  44. PROTEINASE INHIBITORY MECHANISMS OF SERPINS
    Guy Salvesen; Fiscal Year: 2003
    ..Predominant in this are the serpins, members of an evolutionary related superfamily that are demonstrably responsible for regulating the ..
  45. New Function for the Serpin PAI-2 as a Regulator of pRb
    Toni Antalis; Fiscal Year: 2007
    ..type 2 (PAl-2) is structurally and functionally a member of a large family of serine protease inhibitors or serpins. Serpins are key regulators of important biological processes such as complement activation, fibrinolysis, ..
  46. Mediators of Toxoplasma surviral during infection
    VERNON CARRUTHERS; Fiscal Year: 2004
    ..Our central hypothesis is that Toxoplasma uses natural serine proteases (serpins) to control innate immune defenses including inflammation and complement fixation via the alternative pathway...
  47. STRUCTURAL MOTIFS AND PLASMINOGEN ACTIVATOR
    James Quigley; Fiscal Year: 1999
    ..chuPA manifests its activity in an uncontrolled, unregulated manner: It is insensitive to the known uPA-specific serpins, it accumulates in plasminogen-free cultures as active enzyme, and most unusually it is activated by an ..
  48. BIOLOGY OF STR-3 AND ITS ROLE IN LUNG CANCER
    Ian Anderson; Fiscal Year: 1999
    ..MMP structure, the enzyme has a unique substrate specificity, hydrolyzing certain serine protease inhibitors (serpins) including alpha1 anti-trypsin (alpha1 proteinase inhibitor, alpha1-PI)...
  49. Development of a Tumor Selective Replicating Vaccinia
    David Bartlett; Fiscal Year: 2007
    ..The aims of this study are 1.) Enhance tumor selectivity and safety by combining deletions of vaccinia serpins with TK and VGF, and define the mechanism of tumor selective replication...
  50. FENIB: A familial seizure disorder
    PETER HOLOHAN; Fiscal Year: 2003
    ..FENIB shares a common molecular pathophysiology with other mutated serpins, i.e...
  51. MOLECULAR INTERACTIONS REGULATING SERPIN FUNCTION
    Daniel Lawrence; Fiscal Year: 2006
    ..b>Serpins are involved in the regulation of such diverse processes as coagulation, fibrinolysis, complement activation, ..
  52. GORDON CONFERENCE ON PROTEASES/INHIBITORS
    SALVATORE PIZZO; Fiscal Year: 1992
    ..to specifics of protease mechanisms (Ben Dunn, Chairman), 2 to serine protease inhibitors of the plasma (Serpins) (Robin Carrell, Chairman), one to effector modules of proteases (Frank Castellino, Chairman), one to protease ..
  53. Amyloids and Other Abnormal Protein Folding Process
    Ron Kopito; Fiscal Year: 2002
    ..expansion diseases and nonneurological diseases like liver disease that accompanies the misfolding of serpins. This conference will integrate discussions of advances in understanding the structural basis for misfolding and ..
  54. QTOF Ultima API Hybrid Quadraupole/Orthogonal MS
    Sheldon Schuster; Fiscal Year: 2003
    ..that proteins play in apoptosis, still another (Moyer) is looking to define the structure of poxvirus encoded serpins. (Hargrave) is looking to better understand the proteins that bind to rhodopsin and the role of adhesion related ..
  55. Structural Mechanisms for the Inhibition of Thrombosis
    JAMES HUNTINGTON; Fiscal Year: 2009
    ..of thrombin formation through inhibition of upstream coagulation factor Xa;2) direct inhibition of thrombin by serpins antithrombin (AT) and heparin cofactor II (HCII);and, 3) attenuation of thrombin's procoagulant activity ..
  56. Structural examination of serpin-protein interactions
    PETER GETTINS; Fiscal Year: 2009
    ..Kazal, and Bowman-Birk families make do with lock-and-key type interactions to inhibit target proteinases, serpins have now been shown by x-ray crystallography, NMR spectroscopy and FRET to employ a remarkable conformational ..
  57. FUNCTION AND DYSFUNCTION IN HUMAN ANTITHROMBINS
    PETER GETTINS; Fiscal Year: 2007
    ..For antithrombins that have been activated by mutation,[unreadable] x-ray crystallography, through collaboration with Dr. Robin Carrell,[unreadable] will be used.[unreadable]..
  58. 900MHz NMR for Structural Biology in Chicago
    PETER GETTINS; Fiscal Year: 2007
    ..As part of the facility, a resource will be established for development of procedures for intein-based segmental isotopic labeling of proteins, as well as for production of segmentally labeled DNA and RNA species. ..
  59. ACQUISITION OF CRYOPROBE FOR 600 MHZ NMR SPECTROMETER
    PETER GETTINS; Fiscal Year: 2001
    ..Olson, with interests in serpin inhibition mechanism, Dr. Patston, with interests in the structure of the serpin angiotensinogen, and Dr. Silver, who is characterizing a unique silver binding protein, silE. ..
  60. 3rd Intl Symp on Serpin Biology, Structure and Function
    PETER GETTINS; Fiscal Year: 2002
    Partial support is requested for the 3rd International Symposium on the biology, structure, and function of serpins, to be held in Chicago, Illinois June 2-5, 2002...
  61. ULTRASENSITIVE CALORIMETRY SYSTEM FOR BIOMOLECULES
    PETER GETTINS; Fiscal Year: 2001
    ..presence of calcium, (vi) heparin binding to antithrombin variants, (vii) interaction of antithrombin and other serpins with target proteinases, (viii) stability of native and cleaved serpins, (viii) binding of hormone to thyroxine ..
  62. Protein interactions by analytical ultracentrifugation
    PETER GETTINS; Fiscal Year: 2007
    ..The knowledge gained will be invaluable for design of therapeutics against such infections or in amelioration of diseases associated with aberrant functioning of processes such as blood coagulation. [unreadable] [unreadable] [unreadable]..
  63. MOLECULAR BASIS OF COAGULATION PROTEASE SPECIFICITY
    Alireza R Rezaie; Fiscal Year: 2010
    ....