RESEARCH CENTER FOR PHARMACOLOGY AND DRUG TOXICOLOGY

Summary

Principal Investigator: L Jackson Roberts
Abstract: The Research Center for Pharmacology and Drug Toxicology: Novel Mechanisms and Pharmacological Consequences of Polyunsaturated Fatty Acid Oxygenation brings together a tightly-knit group of experienced investigators with a shared interest in polyunsaturated fatty acid oxygenation to undertake research focused on the pharmacology, biochemistry, and biology of eicosanoids and related compounds. The goal of this research is to identify new targets for the development of therapies to modulate the formation, metabolism, and biological activities of eicosanoids and related compounds in humans. Studies suggest that oxygenated polyunsaturated fatty acid species play an important role in human physiology and pathophysiology. Thus, pharmacological manipulation of the formation of oxidized species of fatty acids provides the opportunity to prevent or treat pathophysiological processes associated with these compounds. Nonetheless, a thorough understanding, at the molecular level, of factors influencing the formation and actions of eicosanoids and related compounds remains elusive. This Center comprises five research projects and two cores that will provide important insights into the role of oxygenated species of polyunsaturated fatty acids, derived either enzymatically or non-enzymatically, in human physiology and pathophysiology. A strength of our research program is that proposed projects integrate basic pharmacological, biochemical and molecular biological approaches with translational studies involving humans. Project 1 will define biochemical pathways involved in the formation of novel glyceryl-prostaglandins (PGs) from 2-arachidonylglycerol, examine their generation in cells and tissues, and characterize their metabolism in vivo. Project 2 will test the hypothesis that PGD2 receptors are critical modulators of inflammation in the central nervous system using a variety of in vitro and in vivo models. Project 3 builds on findings that acetaminophen inhibits heme protein-catalyzed lipid peroxidation and will determine the molecular basis for this effect. In addition, studies will evaluate the inhibition of lipid peroxidation by acetaminophen-based regimens in humans with subarachnoid hemorrhage. 4-hydroxynonenal is a bioactive lipid derived from the fragmentation of peroxidized polyunsaturated fatty acids that mediates adverse effects of oxidant stress. Project 4 will focus on mechanisms by which this compound is formed in vivo and characterize novel HNE adducts. Project 5 will test the hypothesis that the oxidation of docosahexaenoic can be precisely defined in humans and leads to the formation of here-to-fore undescribed, biologically active, products containing complex cyclic structures. These studies will utilize DNA esterified in phosphatidylethanolamine, a biologically relevant form of this fatty acid. The investigators included in this research proposal are highly integrated both scientifically and intellectually and are extremely experienced in a number of facets of research related to the oxygenation of arachidonate and other polyunsaturated fatty acids. It is anticipated that the projects proposed will significantly advance our understanding of the pharmacology and biology of eicosanoids and related compounds.
Funding Period: ----------------1997 - ---------------2011-
more information: NIH RePORT

Top Publications

  1. pmc Markers of oxidative stress and systemic vasoconstriction in pregnant women drinking > or =48 g of alcohol per day
    Caroline Signore
    Epidemiology Branch, Division of Epidemiology, Statistics, and Prevention Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892, USA
    Alcohol Clin Exp Res 32:1893-8. 2008
  2. ncbi Correlation of F4-neuroprostanes levels in cerebrospinal fluid with outcome of aneurysmal subarachnoid hemorrhage in humans
    Yu Ping Hsieh
    Graduate Institute of Medical Biotechnology Department of Medical Biotechnology and Laboratory Science, College of Medicine, Chang Gung University, Tao Yuan, Taiwan
    Free Radic Biol Med 47:814-24. 2009
  3. ncbi The 1.85 A structure of an 8R-lipoxygenase suggests a general model for lipoxygenase product specificity
    David B Neau
    Department of Biological Sciences, Louisiana State University, Baton Rouge, Louisiana 70803, USA
    Biochemistry 48:7906-15. 2009
  4. pmc Quantification of F2-isoprostanes as a reliable index of oxidative stress in vivo using gas chromatography-mass spectrometry (GC-MS) method
    Wei Liu
    Department of Chemistry, Vanderbilt University, Nashville, TN 37235, USA
    Free Radic Biol Med 47:1101-7. 2009
  5. ncbi New techniques to detect oxidative stress markers: mass spectrometry-based methods to detect isoprostanes as the gold standard for oxidative stress in vivo
    Huiyong Yin
    Division of Clinical Pharmacology, Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN 37232 6602, USA
    Biofactors 34:109-24. 2008
  6. pmc Two pathways for cyclooxygenase-2 protein degradation in vivo
    Masayuki Wada
    Department of Biological Chemistry, University of Michigan, Ann Arbor, Michigan 48109, USA
    J Biol Chem 284:30742-53. 2009
  7. pmc Elevated levels of urinary prostaglandin e metabolite indicate a poor prognosis in ever smoker head and neck squamous cell carcinoma patients
    Vikram D Kekatpure
    Department of Medicine, Weill Cornell Medical College, New York, New York 10065, USA
    Cancer Prev Res (Phila) 2:957-65. 2009
  8. pmc Dietary fish oil exerts hypolipidemic effects in lean and insulin sensitizing effects in obese LDLR-/- mice
    Viswanathan Saraswathi
    Department of Molecular Physiology and Biophysics, Vanderbilt University Medical Center, Nashville, Tennessee 37232, USA
    J Nutr 139:2380-6. 2009
  9. ncbi Simultaneous analysis of multiple lipid oxidation products in vivo by liquid chromatographic-mass spectrometry (LC-MS)
    Huiyong Yin
    Division of Clinical Pharmacology, Department of Medicine, Vanderbilt University, Nashville, TN, USA
    Methods Mol Biol 610:375-86. 2010
  10. pmc Acetaminophen inhibits hemoprotein-catalyzed lipid peroxidation and attenuates rhabdomyolysis-induced renal failure
    Olivier Boutaud
    Department of Pharmacology, Medicine, and Chemistry, Vanderbilt University, Nashville, TN 37232, USA
    Proc Natl Acad Sci U S A 107:2699-704. 2010

Scientific Experts

  • Dawn C Newcomb
  • Claus Schneider
  • Xianwu Li
  • Sachin Patel
  • ALAN BRASH
  • Huiyong Yin
  • Sean S Davies
  • Marshall Glesby
  • Olivier Boutaud
  • Jason D Downey
  • Jason D Morrow
  • Ginger L Milne
  • Lawrence J Marnett
  • Richard M Breyer
  • John A Oates
  • R Stokes Peebles
  • Carol A Rouzer
  • L Jackson Roberts
  • William E Boeglin
  • Erik S Musiek
  • Jing Jin
  • Daniel J Hermanson
  • Joshua D Brooks
  • Kasia Goleniewska
  • Steven R McAnulty
  • Vladimir R Babaev
  • Ling Gao
  • Thomas J Montine
  • Ned A Porter
  • Nathaniel C Gilbert
  • Weisong Zhou
  • C Dirk Keene
  • Viswanathan Saraswathi
  • Martin L Moore
  • Gregor Leibundgut
  • Philip J Kingsley
  • Giuseppe Zanoni
  • Joel Musee
  • Chandramohan Natarajan
  • Daniel E Dulek
  • David C Nieman
  • Kelsey C Duggan
  • David B Neau
  • Wei Liu
  • VALERIE B O'DONNELL
  • Macrae F Linton
  • Sergio Fazio
  • J D Morrow
  • David H Adler
  • BethAnn McLaughlin
  • Giovanni Vidari
  • Shu Xu
  • Alyssa H Hasty
  • Lisa S McAnulty
  • Gladys Block
  • Surajit Banerjee
  • Shinji Toki
  • Sudhansu K Dey
  • Matthew T Lotz
  • Raymond C Harris
  • Ming Zhi Zhang
  • Robert B Cotton
  • Matthew M Huckabee
  • Sue G Bartlett
  • Garret A Fitzgerald
  • Marcia E Newcomer
  • Irene Zagol-Ikapitte
  • Klarissa D Hardy
  • Matthew D Breyer
  • Pingsheng Wu
  • Cecilia P Chung
  • Enrico M Brunoldi
  • Jeffery J Prusakiewicz
  • Jason Morrow
  • Ingrid Avalos
  • Jonathan Morton
  • David M Aronoff
  • Charles L Dumke
  • Andrew Vila
  • Peter B Anning
  • Jing Wu
  • Matthew A Windsor
  • Li Jiang
  • Joseph L Witztum
  • Maceler Aldrovandi
  • Yuxiang Zheng
  • Sotirios Tsimikas
  • Roy Zent
  • Ganesan Murali
  • Michael S Boger

Detail Information

Publications180 found, 100 shown here

  1. pmc Markers of oxidative stress and systemic vasoconstriction in pregnant women drinking > or =48 g of alcohol per day
    Caroline Signore
    Epidemiology Branch, Division of Epidemiology, Statistics, and Prevention Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892, USA
    Alcohol Clin Exp Res 32:1893-8. 2008
    ..Our objective was to compare the levels of urinary markers of oxidative stress and systemic vasoconstriction between women consuming large amounts of alcohol during pregnancy and women who did not drink alcohol during pregnancy...
  2. ncbi Correlation of F4-neuroprostanes levels in cerebrospinal fluid with outcome of aneurysmal subarachnoid hemorrhage in humans
    Yu Ping Hsieh
    Graduate Institute of Medical Biotechnology Department of Medical Biotechnology and Laboratory Science, College of Medicine, Chang Gung University, Tao Yuan, Taiwan
    Free Radic Biol Med 47:814-24. 2009
    ..The results first demonstrate oxidative damage to DHA in brain tissue following aSAH and suggest that F(4)-NPs in CSF could be a better predictor for outcome of aSAH than F(2)-IsoPs at early time points...
  3. ncbi The 1.85 A structure of an 8R-lipoxygenase suggests a general model for lipoxygenase product specificity
    David B Neau
    Department of Biological Sciences, Louisiana State University, Baton Rouge, Louisiana 70803, USA
    Biochemistry 48:7906-15. 2009
    ..We demonstrate that mutations within the channel significantly impact enzyme activity and propose a novel model for substrate binding potentially applicable to other members of this enzyme family...
  4. pmc Quantification of F2-isoprostanes as a reliable index of oxidative stress in vivo using gas chromatography-mass spectrometry (GC-MS) method
    Wei Liu
    Department of Chemistry, Vanderbilt University, Nashville, TN 37235, USA
    Free Radic Biol Med 47:1101-7. 2009
    ..The protocol described herein has been optimized and validated to provide the best sensitivity and selectivity for quantification of F(2)-IsoPs from a variety of biological sources...
  5. ncbi New techniques to detect oxidative stress markers: mass spectrometry-based methods to detect isoprostanes as the gold standard for oxidative stress in vivo
    Huiyong Yin
    Division of Clinical Pharmacology, Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN 37232 6602, USA
    Biofactors 34:109-24. 2008
    ..Thus, the complexity of the IsoP pathway has expanded, providing novel insights into mechanisms of lipid peroxidation in vivo and allowing investigators to explore the role of oxidative stress in human disease...
  6. pmc Two pathways for cyclooxygenase-2 protein degradation in vivo
    Masayuki Wada
    Department of Biological Chemistry, University of Michigan, Ann Arbor, Michigan 48109, USA
    J Biol Chem 284:30742-53. 2009
    ..Curiously, WT and Delta 18 COX-2 protein levels are similar in kidneys and spleens from WT and Delta 18 COX-2 mice. There must be compensatory mechanisms to maintain constant COX-2 levels in these tissues...
  7. pmc Elevated levels of urinary prostaglandin e metabolite indicate a poor prognosis in ever smoker head and neck squamous cell carcinoma patients
    Vikram D Kekatpure
    Department of Medicine, Weill Cornell Medical College, New York, New York 10065, USA
    Cancer Prev Res (Phila) 2:957-65. 2009
    ..Possibly, HNSCC patients with high COX-2 activity manifested by elevated urinary PGE-M will benefit from treatment with a COX-2 inhibitor...
  8. pmc Dietary fish oil exerts hypolipidemic effects in lean and insulin sensitizing effects in obese LDLR-/- mice
    Viswanathan Saraswathi
    Department of Molecular Physiology and Biophysics, Vanderbilt University Medical Center, Nashville, Tennessee 37232, USA
    J Nutr 139:2380-6. 2009
    ..Taken together, our data suggest that fish oil reduces hepatic steatosis in both lean and obese mice, has potent plasma lipid lowering effects in lean mice, and exerts insulin sensitizing effects in obese mice...
  9. ncbi Simultaneous analysis of multiple lipid oxidation products in vivo by liquid chromatographic-mass spectrometry (LC-MS)
    Huiyong Yin
    Division of Clinical Pharmacology, Department of Medicine, Vanderbilt University, Nashville, TN, USA
    Methods Mol Biol 610:375-86. 2010
    ..This LC-MS technique can be applied to study the free radical oxidation mechanism in vitro and assess the oxidative stress status in biological tissues and fluids...
  10. pmc Acetaminophen inhibits hemoprotein-catalyzed lipid peroxidation and attenuates rhabdomyolysis-induced renal failure
    Olivier Boutaud
    Department of Pharmacology, Medicine, and Chemistry, Vanderbilt University, Nashville, TN 37232, USA
    Proc Natl Acad Sci U S A 107:2699-704. 2010
    ..These findings also provide a hypothesis for potential therapeutic applications for acetaminophen in diseases involving hemoprotein-mediated oxidative injury...
  11. pmc Structural determinants for calcium mobilization by prostaglandin E2 and prostaglandin F2alpha glyceryl esters in RAW 264.7 cells and H1819 cells
    Robyn Richie-Jannetta
    Department of Biochemistry, Vanderbilt Institute of Chemical Biology, Center in Molecular Toxicology, Vanderbilt University School of Medicine, Nashville, TN 37232 0146, USA
    Prostaglandins Other Lipid Mediat 92:19-24. 2010
    ..This calcium response induced by the glyceryl ester analogs appears to be independent of the putative hydrolysis products, PGE(2) and PGF(2alpha), and appears to represent a novel signaling pathway...
  12. pmc Intra-person variation of urinary biomarkers of oxidative stress and inflammation
    Xiaoyan Wu
    Division of Epidemiology, Vanderbilt University Medical Center, 2525 West End Avenue, Nashville, TN 37203 1738, USA
    Cancer Epidemiol Biomarkers Prev 19:947-52. 2010
    ..However, little information is available regarding the intra-person variation of these biomarkers, hindering their application in epidemiologic studies...
  13. pmc Suppressed accumulation of cerebral amyloid {beta} peptides in aged transgenic Alzheimer's disease mice by transplantation with wild-type or prostaglandin E2 receptor subtype 2-null bone marrow
    C Dirk Keene
    Harborview Medical Center, Box 359645, 325 Ninth Ave, Seattle, WA 98104, USA
    Am J Pathol 177:346-54. 2010
    ..Our results provide a foundation for an adult stem cell-based therapy to suppress soluble Abeta peptide and plaque accumulation in the cerebrum of patients with AD...
  14. pmc Combined vitamin C and vitamin E deficiency worsens early atherosclerosis in apolipoprotein E-deficient mice
    Vladimir R Babaev
    Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN 37232 0475, USA
    Arterioscler Thromb Vasc Biol 30:1751-7. 2010
    ....
  15. pmc Molecular basis for cyclooxygenase inhibition by the non-steroidal anti-inflammatory drug naproxen
    Kelsey C Duggan
    AB Hancock Jr Memorial Laboratory for Cancer Research, Department of Biochemistry, Vanderbilt Institute for Chemical Biology, the Center in Molecular Toxicology, Nashville, Tennessee 37232 0146
    J Biol Chem 285:34950-9. 2010
    ..7 and 2.3 Å resolution, respectively. The combination of mutagenesis, structure analysis, and x-ray crystallography provided comprehensive information on the unique interactions responsible for naproxen binding to COX-2...
  16. pmc Nonsteroidal anti-inflammatory drugs are associated with increased neuritic plaques
    J A Sonnen
    Department of Pathology, University of Washington, Seattle, WA 98104, USA
    Neurology 75:1203-10. 2010
    ..The objective of this study is to determine the relationship between common dementia-associated pathologies and mid- to late-life NSAID exposure...
  17. pmc Nonenzymatic free radical-catalyzed generation of 15-deoxy-Δ(12,14)-prostaglandin J₂-like compounds (deoxy-J₂-isoprostanes) in vivo
    Klarissa D Hardy
    Division of Clinical Pharmacology, Vanderbilt University School of Medicine, Nashville, TN 37232, USA
    J Lipid Res 52:113-24. 2011
    ..4 ± 1.1 ng/g liver) in rats after oxidant insult by CCl₄ treatment, compared with basal levels (0.55 ± 0.21 ng/g liver). These compounds may have important bioactivities in vivo under conditions associated with oxidant stress...
  18. ncbi Analysis of endocannabinoids, their congeners and COX-2 metabolites
    Philip J Kingsley
    A B Hancock, Jr Memorial Laboratory for Cancer Research, Department of Biochemistry, Vanderbilt Institute of Chemical Biology, Vanderbilt University School of Medicine, Nashville, TN 37232, United States
    J Chromatogr B Analyt Technol Biomed Life Sci 877:2746-54. 2009
    ..This review will summarize quantitative analytical methodology as reported in the literature from 1992 to present for the analysis of endocannabinoids and related compounds...
  19. pmc Dietary supplementation of omega-3 fatty acid-containing fish oil suppresses F2-isoprostanes but enhances inflammatory cytokine response in a mouse model of ovalbumin-induced allergic lung inflammation
    Huiyong Yin
    Division of Clinical Pharmacology, Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN 37232, USA
    Free Radic Biol Med 47:622-8. 2009
    ....
  20. pmc Differential regulation of GM1 and asialo-GM1 expression by T cells and natural killer (NK) cells in respiratory syncytial virus infection
    Martin L Moore
    Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee 37232 2650, USA
    Viral Immunol 21:327-39. 2008
    ..Also, GM1/ASGM1-expressing cells are important for control of RSV in BALB/c mice, whereas STAT1(-/-) mice clear RSV by an alternative pathway...
  21. pmc The prostaglandin E2 EP2 receptor accelerates disease progression and inflammation in a model of amyotrophic lateral sclerosis
    Xibin Liang
    Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, CA, USA
    Ann Neurol 64:304-14. 2008
    ..We tested whether EP2 signaling participated in disease pathogenesis in the G93A superoxide dismutase (SOD) model of familial ALS...
  22. ncbi Cyclooxygenase inhibition during allergic sensitization increases STAT6-independent primary and memory Th2 responses
    Weisong Zhou
    Division of Allergy, Pulmonary and Critical Care Medicine, Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN 37232, USA
    J Immunol 181:5360-7. 2008
    ....
  23. pmc NMDA-induced seizure intensity is enhanced in COX-2 deficient mice
    Christopher D Toscano
    Molecular Neuroscience Unit, Brain Physiology and Metabolism Section, National Institute on Aging, National Institutes of Health, Bethesda, MD 20892, USA
    Neurotoxicology 29:1114-20. 2008
    ..Furthermore, increased levels of prostaglandins after seizures are associated with consistent manifestation of neuronal damage...
  24. ncbi The COXIB experience: a look in the rearview mirror
    Lawrence J Marnett
    Department of Biochemistry, Vanderbilt Institute of Chemical Biology, Center in Molecular Toxicology, Vanderbilt University School of Medicine, Nashville, Tennessee 37232 0146, USA
    Annu Rev Pharmacol Toxicol 49:265-90. 2009
    ..This review provides an overview of the discovery, development, and difficulties of the COXIBs, a perspective on what has been learned, and speculation on the way forward...
  25. pmc Cyclooxygenases: structural and functional insights
    Carol A Rouzer
    A B Hancock Jr Memorial Laboratory for Cancer Research, Department of Biochemistry, Vanderbilt Institute of Chemical Biology, Center in Molecular Toxicology, Vanderbilt University School of Medicine, Nashville, TN 37232 0146, USA
    J Lipid Res 50:S29-34. 2009
    ..However, recent discoveries call this paradigm into question and reveal as yet underappreciated functions for both enzymes. This review focuses on some of these new insights...
  26. pmc Isoprostanes
    L Jackson Roberts
    Division of Clinical Pharmacology, Vanderbilt University Medical Center, Nashville, TN, USA
    J Lipid Res 50:S219-23. 2009
    ..These findings will be summarized as well...
  27. pmc Macrophage EP4 deficiency increases apoptosis and suppresses early atherosclerosis
    Vladimir R Babaev
    Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN 37232 6300, USA
    Cell Metab 8:492-501. 2008
    ....
  28. ncbi Thromboxane and isoprostanes as inflammatory and vasoactive mediators in black walnut heartwood extract induced equine laminitis
    Erik Noschka
    Department of Large Animal Clinical Sciences, Virginia Maryland Regional College of Veterinary Medicine Duck Pond Drive, Blacksburg, VA 24071, United States
    Vet Immunol Immunopathol 129:200-10. 2009
    ..Because laminar veins are sensitive to thromboxane and isoprostanes, these substances may act as conduits between the inflammatory and vascular events occurring in laminitis and may be therapeutic targets for this crippling condition...
  29. ncbi Cyclosporine A suppresses keratinocyte cell death through MPTP inhibition in a model for skin cancer in organ transplant recipients
    Kimberly G Norman
    Department of Medicine, Division of Dermatology, VA Tennessee Valley Healthcare System and Vanderbilt University Medical Center, Nashville, TN, USA
    Mitochondrion 10:94-101. 2010
    ..These findings suggest that CsA may promote skin cancer in transplant patients by allowing keratinocyte survival under conditions of increased genotoxic stress...
  30. pmc The enteropathy of prostaglandin deficiency
    David H Adler
    Department of Medicine, Division of Clinical Pharmacology, Vanderbilt University, Vanderbilt Medical Center, 1211 Medical Center Drive, Nashville, TN 37232, USA
    J Gastroenterol 44:1-7. 2009
    ..We present here a genetic deficiency of eicosanoid biosynthesis that illuminates the mechanism of NSAID-induced ulcers of the small intestine...
  31. pmc S1P/S1P2 signaling induces cyclooxygenase-2 expression in Wilms tumor
    Mei Hong Li
    Center for Vascular Biology, University of Connecticut Health Center, Farmington, Connecticut, USA
    J Urol 181:1347-52. 2009
    ..Cyclooxygenase-2 has been reported to be ubiquitously expressed in Wilms tumor, the most common malignant renal tumor in children. However, to our knowledge the regulation mechanism of cyclooxygenase-2 expression remains unexplored...
  32. pmc A chimeric A2 strain of respiratory syncytial virus (RSV) with the fusion protein of RSV strain line 19 exhibits enhanced viral load, mucus, and airway dysfunction
    Martin L Moore
    Department of Pediatrics, Vanderbilt University School of Medicine, Nashville, Tennessee 37232, USA
    J Virol 83:4185-94. 2009
    ..We identified the F protein of RSV line 19 as a factor that plays a role in pulmonary mucin expression in the setting of RSV infection...
  33. pmc A functional IL-13 receptor is expressed on polarized murine CD4+ Th17 cells and IL-13 signaling attenuates Th17 cytokine production
    Dawn C Newcomb
    Department of Medicine, Vanderbilt University Medical Center, Nashville, TN 37232, USA
    J Immunol 182:5317-21. 2009
    ..Therefore, therapeutic intervention inhibiting IL-13 production could have adverse consequences by up-regulating Th17 inflammation in certain disease states...
  34. pmc Protection of hippocampal neurogenesis from toll-like receptor 4-dependent innate immune activation by ablation of prostaglandin E2 receptor subtype EP1 or EP2
    C Dirk Keene
    Department of Pathology, University of Washington, Box 359791, Seattle, WA 98104, USA
    Am J Pathol 174:2300-9. 2009
    ....
  35. pmc Low-Sodium DASH reduces oxidative stress and improves vascular function in salt-sensitive humans
    Y Al-Solaiman
    Department of Medicine, Medical University of South Carolina, Charleston, SC 29425, USA
    J Hum Hypertens 23:826-35. 2009
    ..The results suggest that LS-DASH decreases oxidative stress, improves vascular function and lowers blood pressure in SS but not SR volunteers...
  36. pmc 20-Hydroxylation is the CYP-dependent and retinoid-inducible leukotriene B4 inactivation pathway in human and mouse skin cells
    Liping Du
    Department of Biochemistry, Vanderbilt University School of Medicine, Nashville, TN 37232 0146, USA
    Arch Biochem Biophys 484:80-6. 2009
    ..We conclude 20-hydroxylation is the major CYP-dependent LTB4 inactivation pathway in skin; this retinoid-inducible metabolic pathway has capacity to modulate tissue levels of pro-inflammatory lipids...
  37. pmc Selective macrophage ascorbate deficiency suppresses early atherosclerosis
    Vladimir R Babaev
    Department of Medicine, Vanderbilt University Medical Center, Nashville, TN 37232, USA
    Free Radic Biol Med 50:27-36. 2011
    ....
  38. pmc The structure of human 5-lipoxygenase
    Nathaniel C Gilbert
    Department of Biological Sciences, Louisiana State University, Baton Rouge, LA 70803, USA
    Science 331:217-9. 2011
    ..Here, we report the crystal structure at 2.4 angstrom resolution of human 5-LOX stabilized by replacement of this sequence...
  39. pmc Inactivation of the E-prostanoid 3 receptor attenuates the angiotensin II pressor response via decreasing arterial contractility
    Lihong Chen
    Department of Physiology and Pathophysiology, Peking University Health Science Center, Haidian District, Beijing, China
    Arterioscler Thromb Vasc Biol 32:3024-32. 2012
    ..The present studies aimed at elucidating the role of prostaglandin E(2) receptor subtype 3 (E-prostanoid [EP] 3) in regulating blood pressure...
  40. pmc Extracellular loop II modulates GTP sensitivity of the prostaglandin EP3 receptor
    Chandramohan Natarajan
    Division of Nephrology, Vanderbilt University School of Medicine, S3223 MCN, 1161 21st Avenue, Nashville, TN 37232 2372, USA
    Mol Pharmacol 83:206-16. 2013
    ..This suggests that for the mutant receptors, ECII plays a critical role in linking the agonist bound receptor conformation to the G protein nucleotide bound state...
  41. pmc Development of an in vivo active, dual EP1 and EP3 selective antagonist based on a novel acyl sulfonamide bioisostere
    Jason D Downey
    Department of Pharmacology, Vanderbilt University School of Medicine, Nashville, TN 37232, USA
    Bioorg Med Chem Lett 23:37-41. 2013
    ..Compound 17 represents a potentially novel therapeutic in the treatment of hypertension and diabetes mellitus...
  42. pmc Biosynthesis, isolation, and NMR analysis of leukotriene A epoxides: substrate chirality as a determinant of the cis or trans epoxide configuration
    Jing Jin
    Department of Pharmacology and the Vanderbilt Institute of Chemical Biology, Vanderbilt University, Nashville, TN 37232, USA
    J Lipid Res 54:754-61. 2013
    ....
  43. pmc IL-17A induces signal transducers and activators of transcription-6-independent airway mucous cell metaplasia
    Dawn C Newcomb
    Department of Medicine, Vanderbilt University Medical Center, Nashville, TN 37232, USA
    Am J Respir Cell Mol Biol 48:711-6. 2013
    ..STAT6 KO mTECs showed increased periodic acid-Schiff staining with IL-17A but not with IL-13. Thus, asthma therapies targeting STAT6 may increase IL-17A protein expression, without preventing IL-17A-induced mucus production...
  44. pmc IL-17A inhibits airway reactivity induced by respiratory syncytial virus infection during allergic airway inflammation
    Dawn Catherine Newcomb
    Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee 37232, USA
    Thorax 68:717-23. 2013
    ..Furthermore, interleukin 17A (IL-17A) was only increased in OVA/RSV mice...
  45. pmc Oxidation-specific epitopes and immunological responses: Translational biotheranostic implications for atherosclerosis
    Gregor Leibundgut
    Department of Medicine, University of California San Diego, La Jolla, CA, USA
    Curr Opin Pharmacol 13:168-79. 2013
    ....
  46. pmc PGI₂ signaling inhibits antigen uptake and increases migration of immature dendritic cells
    Shinji Toki
    Pulmonary, and Critical Care Medicine, Vanderbilt University Medical Center, 1161 21st Ave, T 1218 MCN, Nashville, TN 37232 2650, USA
    J Leukoc Biol 94:77-88. 2013
    ..Our results suggest PGI2-IP signaling increases immature DC migration to the draining LNs and may represent a novel mechanism by which this eicosanoid inhibits immune responses...
  47. pmc Demonstration of HNE-related aldehyde formation via lipoxygenase-catalyzed synthesis of a bis-allylic dihydroperoxide intermediate
    Jing Jin
    Department of Pharmacology and the Vanderbilt Institute of Chemical Biology, Vanderbilt University, Nashville, Tennessee 37232, USA
    Chem Res Toxicol 26:896-903. 2013
    ..These findings identify a plausible mechanism that could contribute to the production of 4-hydroxy-alkenals in vivo...
  48. pmc Epithelial-specific deletion of 11β-HSD2 hinders Apcmin/+ mouse tumorigenesis
    Li Jiang
    Departments of Medicine and Cancer Biology, S 3206, MCN, Vanderbilt University Medical Center, Nashville, TN 37232
    Mol Cancer Res 11:1040-50. 2013
    ....
  49. pmc Determinants of binding of oxidized phospholipids on apolipoprotein (a) and lipoprotein (a)
    Gregor Leibundgut
    Departments of Medicine, University of California, San Diego, La Jolla, CA
    J Lipid Res 54:2815-30. 2013
    ..E06 immunoreactivity, reflecting pro-inflammatory OxPLs accessible to the immune system, is strongly influenced by KIV10 LBS and is unique to human apo(a), which may explain Lp(a)'s pro-atherogenic potential. ..
  50. pmc Human platelets generate phospholipid-esterified prostaglandins via cyclooxygenase-1 that are inhibited by low dose aspirin supplementation
    Maceler Aldrovandi
    Institute of Infection and Immunity, School of Medicine, Cardiff University
    J Lipid Res 54:3085-97. 2013
    ..In summary, COX-1 in human platelets acutely mediates membrane phospholipid oxidation via formation of PG-esterified PLs in response to pathophysiological agonists...
  51. pmc Substrate-selective COX-2 inhibition decreases anxiety via endocannabinoid activation
    Daniel J Hermanson
    A B Hancock Jr Memorial Laboratory for Cancer Research, Department of Biochemistry, Vanderbilt Institute of Chemical Biology, Center in Molecular Toxicology, and Vanderbilt Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, Tennessee, USA
    Nat Neurosci 16:1291-8. 2013
    ..Our data suggest a key role for COX-2 in the regulation of eCB signaling and indicate that substrate-selective pharmacology represents a viable approach for eCB augmentation with broad therapeutic potential. ..
  52. pmc Th17-mediated inflammation in asthma
    Dawn C Newcomb
    Vanderbilt University Medical Center, Department of Medicine, Nashville, TN 37232, United States Electronic address
    Curr Opin Immunol 25:755-60. 2013
    ..However, the role of Th17 cells in asthma will be answered in ongoing clinical trials with therapeutics targeting IL-17A and IL-17 receptor signaling. ..
  53. pmc Exploring the molecular determinants of substrate-selective inhibition of cyclooxygenase-2 by lumiracoxib
    Matthew A Windsor
    A B Hancock Jr Memorial Laboratory for Cancer Research, Department of Biochemistry, Department of Chemistry, Department of Pharmacology, Vanderbilt Institute of Chemical Biology, Center in Molecular Toxicology, and Vanderbilt Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, TN, United States
    Bioorg Med Chem Lett 23:5860-4. 2013
    ..The positioning of critical substituents in the binding site was identified from a 2.35Å crystal structure of lumiracoxib bound to COX-2. ..
  54. pmc Inflammation and mechanical stretch promote aortic stiffening in hypertension through activation of p38 mitogen-activated protein kinase
    Jing Wu
    From the Division of Clinical Pharmacology J W, S R T, A K, D W T, M A S, L X, M S M, W C, D G H, and Departments of Medicine and Pharmacology J W, D G H, Vanderbilt University, Nashville, TN and Department of Pharmacology and Toxicology, Faculty of Pharmacy, Mansoura University, Egypt M A S
    Circ Res 114:616-25. 2014
    ..Hypertension is also associated with vascular inflammation and increased mechanical stretch. The interplay between inflammation, mechanical stretch, and aortic stiffening in hypertension remains undefined...
  55. pmc Oxicams bind in a novel mode to the cyclooxygenase active site via a two-water-mediated H-bonding Network
    Shu Xu
    From the A B Hancock Jr Memorial Laboratory for Cancer Research, Departments of Biochemistry, Chemistry, and Pharmacology, Vanderbilt Institute of Chemical Biology, Center in Molecular Toxicology, Vanderbilt Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, Tennessee 37232
    J Biol Chem 289:6799-808. 2014
    ....
  56. pmc EP1 disruption attenuates end-organ damage in a mouse model of hypertension
    Christina S Bartlett
    Department of Pharmacology, Vanderbilt University Medical Center, 1161 21 Ave, Medical Center North B3214, Nashville, TN 37232 2372, USA
    Hypertension 60:1184-91. 2012
    ..Thus, reduction in blood pressure by disruption of EP1 reduced incidence of mortality and decreased organ damage, suggesting that EP1 receptor blockade may be a viable target for antihypertensive therapy...
  57. pmc Prostaglandin H synthase-2-catalyzed oxygenation of 2-arachidonoylglycerol is more sensitive to peroxide tone than oxygenation of arachidonic acid
    Joel Musee
    A B Hancock Jr Memorial Laboratory for Cancer Research, Department of Biochemistry, Vanderbilt Institute of Chemical Biology, Center in Molecular Toxicology, Vanderbilt University School of Medicine, Nashville, Tennessee 37232 0146, USA
    J Biol Chem 287:37383-94. 2012
    ..GPx4 silencing led to 2-4-fold increases in PG-G formation but no change in PG formation. Thus, cellular peroxide tone may be an important determinant of the extent of endocannabinoid oxygenation by PGHS-2...
  58. pmc Nitroarachidonic acid, a novel peroxidase inhibitor of prostaglandin endoperoxide H synthases 1 and 2
    Andrés Trostchansky
    Departamento de Bioquímica and Center for Free Radical and Biomedical Research, Facultad de Medicina, Montevideo, Uruguay
    J Biol Chem 286:12891-900. 2011
    ..In activated human platelets, AANO(2) significantly decreased PGHS-1-dependent thromboxane B(2) formation in parallel with a decrease in platelet aggregation, thus confirming the biological relevance of this novel inhibitory pathway...
  59. pmc Viruses and asthma
    Daniel E Dulek
    Department of Pediatrics, Division of Pediatric Infectious Diseases, Monroe Carell Jr Children s Hospital at Vanderbilt, Vanderbilt University Medical Center, Nashville, TN 37232 2650, USA
    Biochim Biophys Acta 1810:1080-90. 2011
    ..Over the last 20years much effort has been put into clarifying the role that viral respiratory infections play in the eventual development of asthma...
  60. ncbi Biomarker responses and disease susceptibility in juvenile rainbow trout Oncorhynchus mykiss fed a high molecular weight PAH mixture
    C F Bravo
    Department of Environmental and Molecular Toxicology, Oregon State University, Corvallis, Oregon, USA
    Environ Toxicol Chem 30:704-14. 2011
    ..These results link PAH exposure to biomarker responses that may be useful as early indicators of population level responses, such as mortality resulting from an increase in disease susceptibility...
  61. pmc Suppressed microglial E prostanoid receptor 1 signaling selectively reduces tumor necrosis factor alpha and interleukin 6 secretion from toll-like receptor 3 activation
    Xianwu Li
    Department of Pathology, University of Washington, Seattle, Washington, USA
    Glia 59:569-76. 2011
    ..In combination with the ability of EP1 suppression to ameliorate excitotoxicity, these data point to blockade of EP1 as an attractive candidate therapeutic for neurodegenerative diseases...
  62. pmc Intrarenal dopamine deficiency leads to hypertension and decreased longevity in mice
    Ming Zhi Zhang
    Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee 37232, USA
    J Clin Invest 121:2845-54. 2011
    ..Decreasing intrarenal dopamine subjects the kidney to unbuffered responses to Ang II and results in the development of hypertension and a dramatic decrease in longevity...
  63. pmc Bacteria and asthma: more there than we thought
    Daniel E Dulek
    Department of Pediatrics, Division of Pediatric Infectious Diseases, Monroe Carell Jr, Children s Hospital at Vanderbilt, Vanderbilt University Medical Center, Nashville, TN, USA
    Expert Rev Respir Med 5:329-32. 2011
    ..Although several limitations are present, this study provides an intriguing initial insight into the possible relationship between the airway microbiota and asthma pathogenesis...
  64. pmc High-throughput quantification of bioactive lipids by MALDI mass spectrometry: application to prostaglandins
    Joseph D Manna
    Department of Biochemistry, Vanderbilt Institute of Chemical Biology, Mass Spectrometry Research Center, Vanderbilt University School of Medicine, Nashville, Tennessee 37232, USA
    Anal Chem 83:6683-8. 2011
    ..99). The method was adapted for high-throughput screening methods for enzymology and drug discovery. Application to cellular metabolomics was also demonstrated...
  65. pmc Prostaglandin E2 modulation of blood pressure homeostasis: studies in rodent models
    Christina E Swan
    Department of Pharmacology, Vanderbilt University Medical Center, Nashville, TN 37232 2372, USA
    Prostaglandins Other Lipid Mediat 96:10-3. 2011
    ..This review focuses on the current understanding of the roles of PGE(2) receptors in vascular reactivity, hypertension and end-organ damage...
  66. pmc The fatty acid oxidation product 15-A3t-isoprostane is a potent inhibitor of NFκB transcription and macrophage transformation
    Joshua D Brooks
    Division of Clinical Pharmacology, Vanderbilt University Medical Center, Nashville, Tennessee 37232 8548, USA
    J Neurochem 119:604-16. 2011
    ....
  67. pmc Cannabinoids, endocannabinoids, and cancer
    Daniel J Hermanson
    AB Hancock Jr Memorial Laboratory for Cancer Research, Departments of Biochemistry, Vanderbilt Institute of Chemical Biology, Center in Molecular Toxicology, Vanderbilt Ingram Comprehensive Cancer Center, Vanderbilt University School of Medicine, Nashville, TN 37232 0146, USA
    Cancer Metastasis Rev 30:599-612. 2011
    ..The antiproliferative and apoptotic effects produced by some of these pharmacological probes reveal that the endocannabinoid system is a promising new target for the development of novel chemotherapeutics to treat cancer...
  68. pmc (R)-Profens are substrate-selective inhibitors of endocannabinoid oxygenation by COX-2
    Kelsey C Duggan
    Department of Biochemistry, Vanderbilt University School of Medicine, Nashville, Tennessee, USA
    Nat Chem Biol 7:803-9. 2011
    ....
  69. pmc Prostaglandin I2 signaling drives Th17 differentiation and exacerbates experimental autoimmune encephalomyelitis
    Weisong Zhou
    Division of Allergy, Pulmonary and Critical Care Medicine, Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee, United States of America
    PLoS ONE 7:e33518. 2012
    ..Although PGI(2) signaling suppressed Th1 and Th2 immune responses, the role of PGI(2) in Th17 differentiation is not known...
  70. pmc Acetaminophen inhibits cytochrome c redox cycling induced lipid peroxidation
    Huiyong Yin
    Department of Medicine, Division of Clinical Pharmacology, Vanderbilt University School of Medicine, TN 37232, USA
    Biochem Biophys Res Commun 423:224-8. 2012
    ..Our study also provides a potentially novel pharmacological approach for inhibiting the cascade of events that can result from redox cycling of cyt c...
  71. pmc Mechanisms of respiratory syncytial virus modulation of airway immune responses
    Matthew T Lotz
    Department of Medicine, Division of Allergy, Pulmonary and Critical Care Medicine, Vanderbilt University School of Medicine, Nashville, TN 37232 2650, USA
    Curr Allergy Asthma Rep 12:380-7. 2012
    ..In addition, effective immune system regulation of IL-10 expression and T regulatory cell (Treg) airway accumulation are essential for effective RSV clearance...
  72. pmc Fish oil and indomethacin in combination potently reduce dyslipidemia and hepatic steatosis in LDLR(-/-) mice
    Ganesan Murali
    Division of Diabetes, Endocrinology and Metabolism, University of Nebraska Medical Center and VA Nebraska Western Iowa Health Care System, Omaha, NE, USA
    J Lipid Res 53:2186-97. 2012
    ..Moroever, the nuclear level of PXR is significantly increased in FO + Indo group. Combining FO with COXIBs may exert their beneficial effects on inflammation and lipid metabolism via PXR and cytochrome P450...
  73. pmc Therapeutic targets in prostaglandin E2 signaling for neurologic disease
    P J Cimino
    Division of Neuropathology, University of Washington School of Medicine, Box 359791, Harborview Medical Center, Seattle, WA 98104, USA
    Curr Med Chem 15:1863-9. 2008
    ..However promising these preclinical studies are, they have yet to be followed by clinical trials targeting any EP receptor in neurologic diseases...
  74. ncbi Changes in urinary dinor dihydro F(2)-isoprostane metabolite concentrations, a marker of oxidative stress, during and following asthma exacerbations
    Pingsheng Wu
    Department of Medicine and the Division of Allergy, Pulmonary and Critical Care Medicine, Vanderbilt University School of Medicine, Nashville, TN 37232, USA
    Free Radic Res 41:956-62. 2007
    ..Urinary F(2)-IsoP-M may be a clinically useful, simple non-invasive systemic measure of oxidative stress in asthmatics, providing information not captured by spirometry or symptoms...
  75. ncbi Energy expenditure, inflammation, and oxidative stress in steady-state adolescents with sickle cell anemia
    Sylvie A Akohoue
    Center for Nutrition and Department of Family and Community Medicine, Meharry Medical College, Nashville, Tennessee 37208, USA
    Pediatr Res 61:233-8. 2007
    ..778; p < 0.001). Low-grade inflammation and increased oxidative stress are present in adolescents with HbSS in the absence of acute crisis, and their markers are correlated with elevated REE...
  76. ncbi Ethanol self-administration and alterations in the livers of the cynomolgus monkey, Macaca fascicularis
    Priscilla Ivester
    Department of Biochemistry, Wake Forest University School of Medicine, Winston Salem, NC 27157, USA
    Alcohol Clin Exp Res 31:144-55. 2007
    ....
  77. pmc Lipid profiling reveals arachidonate deficiency in RAW264.7 cells: Structural and functional implications
    Carol A Rouzer
    Department of Biochemistry, Center in Molecular Toxicology, Vanderbilt University School of Medicine, Nashville, Tennessee 37232 0146, USA
    Biochemistry 45:14795-808. 2006
    ....
  78. ncbi Novel n-3 fatty acid oxidation products activate Nrf2 by destabilizing the association between Keap1 and Cullin3
    Ling Gao
    Department of Medicine, Division of Clinical Pharmacology, Vanderbilt University School of Medicine, Nashville, Tennessee 37232, USA
    J Biol Chem 282:2529-37. 2007
    ..These experiments provide a biochemical basis for the hypothesis that formation of J-ring compounds generated from oxidation of EPA and DHA in vivo can reach concentrations high enough to induce Nrf2-based cellular defense systems...
  79. ncbi Targeted cyclooxygenase gene (ptgs) exchange reveals discriminant isoform functionality
    Ying Yu
    Institute for Translational Medicine and Therapeutics, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA
    J Biol Chem 282:1498-506. 2007
    ..These mice will provide a valuable reagent with which to elucidate the distinct roles of the COX enzymes in mammalian biology...
  80. ncbi Urinary prostaglandin F2alpha is generated from the isoprostane pathway and not the cyclooxygenase in humans
    Huiyong Yin
    Division of Clinical Pharmacology, Department of Medicine, Vanderbilt University, Nashville, TN 37232, USA
    J Biol Chem 282:329-36. 2007
    ..The elucidation that urinary PGF(2alpha) in humans is derived from the IsoP pathway has implications regarding PG formation and inhibition in vivo...
  81. ncbi In vivo and in vitro lipid peroxidation of arachidonate esters: the effect of fish oil omega-3 lipids on product distribution
    Todd A Davis
    Department of Chemistry, Vanderbilt University, Nashville, TN 37235, USA
    J Am Chem Soc 128:14897-904. 2006
    ..These results suggest that dietary omega-3 PUFAs may influence the formation of bio-active peroxidation products derived from omega-6 PUFAs by channeling the free radical pathway away from the F2-IsoPs...
  82. ncbi Angiotensin II induces interleukin-6 in humans through a mineralocorticoid receptor-dependent mechanism
    James M Luther
    Division of Clinical Pharmacology, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN 37232 6602, USA
    Hypertension 48:1050-7. 2006
    ..In contrast, angiotensin II-induced oxidative stress, as measured by F(2)-isoprostanes, is mineralocorticoid receptor independent and may be pressor dependent...
  83. ncbi Phospholipid-protein adducts of lipid peroxidation: synthesis and study of new biotinylated phosphatidylcholines
    Keri A Tallman
    Department of Chemistry, Department of Biochemistry, and Mass Spectrometry Research Center, Vanderbilt University, Nashville, Tennessee 37235, USA
    Chem Res Toxicol 20:227-34. 2007
    ..Biotinylated lipids such as PLPBSO and modern proteomics tools would appear to provide a new approach to exploring the chemistry and biology of membrane peroxidation associated with oxidative stress...
  84. ncbi Bacterial clearance of Pseudomonas aeruginosa is enhanced by the inhibition of COX-2
    Ruxana T Sadikot
    Department of Veterans Affairs, Jesse Brown VA Hospital, Chicago, IL 60612, USA
    Eur J Immunol 37:1001-9. 2007
    ..Thus it is possible that inhibition of COX-2 or EP2 receptors could be an effective adjunctive treatment for severe or resistant P. aeruginosa pneumonia...
  85. ncbi Oxidative stress in systemic lupus erythematosus: relationship to disease activity and symptoms
    I Avalos
    Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN 37232 6248, USA
    Lupus 16:195-200. 2007
    ..In conclusion, F2 isoprostane excretion is associated with patient-reported symptoms in SLE but not with measures of inflammation, SLEDAI or SLICC. Oxidative stress may contribute to debilitating symptoms such as fatigue in SLE...
  86. ncbi Identification of novel autoxidation products of the omega-3 fatty acid eicosapentaenoic acid in vitro and in vivo
    Huiyong Yin
    Department of Medicine and Pharmacology, Vanderbilt University, Nashville, Tennessee 37232, USA
    J Biol Chem 282:29890-901. 2007
    ..Systematic study of the peroxidation of EPA provides the basis to examine the role of specific oxidation products as mediators of the biological effects of fish oil...
  87. ncbi Hydrolysis of prostaglandin glycerol esters by the endocannabinoid-hydrolyzing enzymes, monoacylglycerol lipase and fatty acid amide hydrolase
    Andrew Vila
    Department of Biochemistry, Vanderbilt Institute of Chemical Biology, Center in Molecular Toxicology, and Vanderbilt Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, Tennessee 37232 0146, USA
    Biochemistry 46:9578-85. 2007
    ..The substrate specificity of AEA compared to those of PG-Gs was approximately 200-300 fold higher for FAAH. Thus, PG-Gs are poor substrates for the major endocannabinoid-degrading enzymes, MGL and FAAH...
  88. ncbi Ibuprofen use during extreme exercise: effects on oxidative stress and PGE2
    Steven R McAnulty
    Department of Health, Leisure, and Exercise Science, Appalachian State University, Boone, NC 28608, USA
    Med Sci Sports Exerc 39:1075-9. 2007
    ..Oxidative stress was examined with use (N = 29) or nonuse (N = 25) of ibuprofen in ultramarathoners after the Western States Endurance Run...
  89. ncbi Fish oil increases cholesterol storage in white adipose tissue with concomitant decreases in inflammation, hepatic steatosis, and atherosclerosis in mice
    Viswanathan Saraswathi
    Department of Molecular Physiology and Biophysics, Vanderbilt University Medical Center, Nashville, TN 37232, USA
    J Nutr 137:1776-82. 2007
    ..05) and decreased atherosclerotic lesion area (P < 0.05). Taken together, these data highlight the specific role of WAT in regulating dietary fish oil-mediated improvement in systemic lipid homeostasis and atherosclerosis...
  90. pmc Control of oxygenation in lipoxygenase and cyclooxygenase catalysis
    Claus Schneider
    Department of Pharmacology, Vanderbilt University, Nashville, TN 37232, USA
    Chem Biol 14:473-88. 2007
    ..We present four mechanistic models, not mutually exclusive, that could account for the specific reactions of molecular oxygen with a fatty acid in the LOX or COX active site...
  91. ncbi A phase I trial to determine the optimal biological dose of celecoxib when combined with erlotinib in advanced non-small cell lung cancer
    Karen L Reckamp
    Department of Medicine, Division of Hematology Oncology, David Geffen School of Medicine at University of California at Los Angeles, 90095, USA
    Clin Cancer Res 12:3381-8. 2006
    ....
  92. pmc Oxidative metabolism of lipoamino acids and vanilloids by lipoxygenases and cyclooxygenases
    Jeffery J Prusakiewicz
    A B Hancock, Jr Memorial Laboratory for Cancer Research, Vanderbilt Institute of Chemical Biology, and Center in Molecular Toxicology, Vanderbilt University School of Medicine, Nashville, TN 37232, USA
    Arch Biochem Biophys 464:260-8. 2007
    ..Fatty acid oxygenases may play an important role in the metabolic inactivation of lipoamino acids or vanilloids or may convert them to bioactive derivatives...
  93. ncbi Lipid profiling reveals glycerophospholipid remodeling in zymosan-stimulated macrophages
    Carol A Rouzer
    Department of Biochemistry, Center in Molecular Toxicology, Vanderbilt University School of Medicine, Nashville, Tennessee 37232 0146, USA
    Biochemistry 46:6026-42. 2007
    ..These results suggest that GPCho is the major ultimate source of 20:4 that is mobilized in zymosan-stimulated RPMs but that 20:4 mobilization may involve the intermediate turnover of alkyl acyl GPEtn species...
  94. ncbi Inhaled nitric oxide attenuates hyperoxic lung injury in lambs
    Robert B Cotton
    Department of Pediatrics, Vanderbilt University Medical Center, Nashville, Tennessee 37232, USA
    Pediatr Res 59:142-6. 2006
    ..However, this study provides no direct evidence that NO is inhibiting CYP-mediated oxidant lung injury...
  95. ncbi Host and direct antitumor effects and profound reduction in tumor metastasis with selective EP4 receptor antagonism
    Li Yang
    Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee, USA
    Cancer Res 66:9665-72. 2006
    ..Selective antagonism of the EP4 receptor may thus represent a novel therapeutic approach for the treatment of cancer and especially its propensity to metastasize...
  96. pmc Expression of COX-2 in platelet-monocyte interactions occurs via combinatorial regulation involving adhesion and cytokine signaling
    Dan A Dixon
    Department of Biological Sciences and South Carolina Cancer Center, University of South Carolina, Columbia, South Carolina 29203, USA
    J Clin Invest 116:2727-38. 2006
    ..These checkpoints may be altered in disease and therefore useful as targets for antiinflammatory intervention...
  97. pmc Cyclopentenone isoprostanes are novel bioactive products of lipid oxidation which enhance neurodegeneration
    Erik S Musiek
    Department of Pharmacology, Venderbilt University, Nashville, Tennessee 37232, USA
    J Neurochem 97:1301-13. 2006
    ..Together these findings suggest that cyclopentenone IsoPs may contribute to neuronal death caused by oxidative insults, and that their activity should perhaps be addressed when designing neuroprotective therapies...