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Genomes and Genes | enzyme inductionSummarySummary: An increase in the rate of synthesis of an enzyme due to the presence of an inducer which acts to derepress the gene responsible for enzyme synthesis. Top Publications
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EMMPRIN/CD147, an MMP modulator in cancer, development and tissue repair
Eric E Gabison
Unité 532 Inserm, Hopital Saint Louis, Paris 75010, France
Biochimie 87:361-8. 2005..This review will discuss the recent findings concerning these diverse regulatory mechanisms in various physiological and pathological situations...Human response to dioxin: aryl hydrocarbon receptor (AhR) molecular structure, function, and dose-response data for enzyme induction indicate an impaired human AhR
Kevin T Connor
Geomatrix, Inc, Folsom, California, USA
J Toxicol Environ Health B Crit Rev 9:147-71. 2006..required approximately 10-fold higher concentrations of TCDD in vitro than rodent cells to respond with enzyme induction. Recent studies of in vivo enzyme induction-related endpoints in human populations with moderately and highly ..IL-17 stimulates MMP-1 expression in primary human cardiac fibroblasts via p38 MAPK- and ERK1/2-dependent C/EBP-beta , NF-kappaB, and AP-1 activation
Dolores M Cortez
Department of Veterans Affairs South Texas Veterans Health Care System, The University of Texas Health Science Center, 7703 Floyd Curl Drive, San Antonio, TX 78229 3900, USA
Am J Physiol Heart Circ Physiol 293:H3356-65. 2007..Our data indicate that IL-17 induces MMP-1 in human cardiac fibroblasts directly via p38 MAPK- and ERK-dependent AP-1, NF-kappaB, and C/EBP-beta activation and suggest that IL-17 may play a critical role in myocardial remodeling...Carbon monoxide induces heme oxygenase-1 via activation of protein kinase R-like endoplasmic reticulum kinase and inhibits endothelial cell apoptosis triggered by endoplasmic reticulum stress
Ki Mo Kim
Department of Immunology, Wonkwang University School of Medicine, Iksan, Chunbug 570 749, Republic of Korea
Circ Res 101:919-27. 2007..Thus, the HO-1/CO system might be potential therapeutics in vascular diseases associated with ER stress...Cytochrome P450 induction by rifampicin in healthy subjects: determination using the Karolinska cocktail and the endogenous CYP3A4 marker 4beta-hydroxycholesterol
K P Kanebratt
Division of Clinical Pharmacology, Department of Laboratory Medicine, Karolinska Institutet, Karolinska University Hospital, Huddinge, Sweden
Clin Pharmacol Ther 84:589-94. 2008..4-fold, P < 0.05; and 4.2-fold, P < 0.01, respectively). In conclusion, we have shown that the Karolinska cocktail and 4beta-hydroxycholesterol can be used for an initial screening of the induction properties of a drug candidate...Dimethylfumarate induces immunosuppression via glutathione depletion and subsequent induction of heme oxygenase 1
Joachim C U Lehmann
CRBA Inflammation, Schering AG, Berlin, Germany
J Invest Dermatol 127:835-45. 2007....Enzyme induction and dietary chemicals as approaches to cancer chemoprevention: the Seventh DeWitt S. Goodman Lecture
Allan H Conney
Susan Lehman Cullman Laboratory for Cancer Research, Department of Chemical Biology, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, 164 Frelinghuysen Road, Piscataway, New Jersey 08854 8020, USA
Cancer Res 63:7005-31. 2003..article describes research from my laboratory and related research from other laboratories on the effects of enzyme induction on chemical carcinogenesis as an approach to cancer chemoprevention, as well as studies on the inhibitory ..Functional expression, inhibition and induction of CYP enzymes in HepaRG cells
Miia Turpeinen
Department of Pharmacology and Toxicology, 90014 University of Oulu, Oulu, Finland
Toxicol In Vitro 23:748-53. 2009..In conclusion, HepaRG cells may be a promising cell line for various applications, which currently employ hepatic subcellular preparations or cultured primary hepatocytes...Effects of prototypical microsomal enzyme inducers on cytochrome P450 expression in cultured human hepatocytes
Ajay Madan
XenoTech, LLC, 16825 West 116th Street, Lenexa, KS 66219, USA
Drug Metab Dispos 31:421-31. 2003....Carbon monoxide protects against liver failure through nitric oxide-induced heme oxygenase 1
Brian S Zuckerbraun
Department of Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA
J Exp Med 198:1707-16. 2003....An essential role for nuclear receptors SXR/PXR in detoxification of cholestatic bile acids
W Xie
Howard Hughes Medical Institute, Gene Expression Laboratory, The Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA
Proc Natl Acad Sci U S A 98:3375-80. 2001..Therefore, we establish SXR and PXR as bile acid receptors and a role for the xenobiotic response in the detoxification of bile acids...Restraint of proinflammatory cytokine biosynthesis by mitogen-activated protein kinase phosphatase-1 in lipopolysaccharide-stimulated macrophages
Peili Chen
Stress Signaling Unit, Laboratory of Cellular and Molecular Biology, National Institute on Aging, Intramural Research Program, National Institutes of Health, Baltimore, MD 21224, USA
J Immunol 169:6408-16. 2002..These findings highlight MKP-1 as a critical negative regulator of the macrophage inflammatory response, underscoring its premise as a potential target for developing novel anti-inflammatory drugs...Role of mitogen-activated protein kinase cascades in mediating lipopolysaccharide-stimulated induction of cyclooxygenase-2 and IL-1 beta in RAW264 macrophages
M Caivano
Medical Research Council Protein Phosphorylation Unit, Department of Biochemistry, University of Dundee, Dundee, United Kingdom
J Immunol 164:3018-25. 2000..They also suggest that MSK1 and MSK2 may play a role in these processes and hence are potential targets for the development of novel antiinflammatory drugs...Expression of drug metabolizing enzymes in hepatocyte-like cells derived from human embryonic stem cells
Monica Ek
Section of Pharmacogenetics, Department of Physiology and Pharmacology, Karolinska Institutet, SE 17177 Stockholm, Sweden
Biochem Pharmacol 74:496-503. 2007....Induction of cyp1a1 is a nonspecific biomarker of aryl hydrocarbon receptor activation: results of large scale screening of pharmaceuticals and toxicants in vivo and in vitro
Wenyue Hu
Iconix Biosciences, Inc, 325 E Middlefield Road, Mountain View, CA 94043, USA
Mol Pharmacol 71:1475-86. 2007....Enhancer-mediated control of macrophage-specific arginase I expression
Anne Laure Pauleau
Department of Infectious Diseases, St Jude Children s Research Hospital, 332 North Lauderdale, Memphis, TN 38105, USA
J Immunol 172:7565-73. 2004..Identification of a powerful extrahepatic regulatory enhancer for arginase I provides potential to manipulate arginase I activity in immune cells while sparing liver urea cycle function...Proline oxidase, encoded by p53-induced gene-6, catalyzes the generation of proline-dependent reactive oxygen species
S P Donald
Division of Basic Science, National Cancer Institute, Frederick, Maryland 21702, USA
Cancer Res 61:1810-5. 2001..We hypothesize that proline oxidation supports the generation of ROS by donating reducing potential to an electron transport chain altered either by p53-dependent mechanisms or by overexpression of POX...Differential regulation of arginases and inducible nitric oxide synthase in murine macrophage cells
S M Morris
Department of Molecular Genetics and Biochemistry, University of Pittsburgh, Pittsburgh, Pennsylvania 15261, USA
Am J Physiol 275:E740-7. 1998..These complex patterns of expression suggest that the arginase isoforms may play distinct, although partially overlapping, functional roles in macrophage arginine metabolism...Antiviral activity and hepatoprotection by heme oxygenase-1 in hepatitis B virus infection
Ulrike Protzer
Molecular Infectiology at Center for Molecular Medicine Cologne, Institute for Medical Microbiology, Immunology, and Hygiene, University of Cologne, Cologne, Germany
Gastroenterology 133:1156-65. 2007..Induction of heme oxygenase-1 (HO-1) has been shown to be beneficial in immune-mediated liver damage. We now investigate the effects of HO-1 induction in models of human hepatitis B virus (HBV) infection...Fungal adenylyl cyclase integrates CO2 sensing with cAMP signaling and virulence
Torsten Klengel
Department of Biosciences, University of Kent, Canterbury, Kent CT2 7NJ, United Kingdom
Curr Biol 15:2021-6. 2005..Novel therapeutic agents could target this pathway at several levels to control fungal infections...Phase 2 enzyme induction by conjugated linoleic acid improves lupus-associated oxidative stress
Paolo Bergamo
Istituto di Scienze dell Alimentazione, Consiglio Nazionale delle Ricerche CNR ISA, Via Roma 52, 83100, Avellino, Italy
Free Radic Biol Med 43:71-9. 2007..In conclusion our data indicate that the activation of detoxifying enzymes may be one of the mechanisms whereby dietary CLA down-regulates oxidative stress in MRL/lpr mice...Induction of drug metabolism: the role of nuclear receptors
Christoph Handschin
Division of Pharmacology Neurobiology, Biozentrum of the University of Basel, Klingelbergstrasse 50 70, CH 4056 Basel, Switzerland
Pharmacol Rev 55:649-73. 2003....Modulation of Nrf2-mediated antioxidant and detoxifying enzyme induction by the green tea polyphenol EGCG
Hye Kyung Na
National Research Laboratory of Molecular Carcinogenesis and Chemoprevention, College of Pharmacy, Seoul National University, Shinlim Dong, Kwanak Ku, Seoul 151 742, South Korea
Food Chem Toxicol 46:1271-8. 2008..This review summarizes the molecular basis of chemoprevention and cytoprotection afforded by EGCG with emphasis on its ability to modulate Nrf2-mediated cellular events...HepaRG human hepatic cell line utility as a surrogate for primary human hepatocytes in drug metabolism assessment in vitro
Marc Lübberstedt
Division of Experimental Surgery, Berlin Brandenburg Center for Regenerative Therapies BCRT, Charite Universitatsmedizin Berlin, Campus Virchow Klinikum, Augustenburger Platz 1, D 13353 Berlin, Germany
J Pharmacol Toxicol Methods 63:59-68. 2011..Due to the limited availability of human liver tissue for cell isolation, there is a need of alternative cell sources for pharmaceutical research...NFAT regulates induction of COX-2 and apoptosis of keratinocytes in response to ultraviolet radiation exposure
R J Flockhart
Institute of Cellular Medicine, Newcastle University, Framlington Pl, Newcastle upon Tyne NE2 4HH, UK
FASEB J 22:4218-27. 2008..Taken together, these data suggest that the proinflammatory, antiapoptotic, and procarcinogenic functions of UV-activated COX-2 may be mediated, in part, by upstream NFAT signaling...Antidepressants: clinically relevant drug interactions to be considered
Rene Schellander
Institute of Experimental and Clinical Pharmacology, Medical University of Graz, Graz, Austria
Pharmacology 86:203-15. 2010..When comparing prescription data and observed adverse drug events, there is fortunately a safety gap between the number of potential drug-drug interactions and the number of clinically observed side effects due to drug-drug interactions...Comparative oxidative metabolism of BDE-47 and BDE-99 by rat hepatic microsomes
Claudio A Erratico
Faculty of Pharmaceutical Sciences, The University of British Columbia, Vancouver, British Columbia, Canada V6T 1Z3
Toxicol Sci 123:37-47. 2011....2-methoxycinnamaldehyde from Cinnamomum cassia reduces rat myocardial ischemia and reperfusion injury in vivo due to HO-1 induction
Jeong Seok Hwa
Department of Urology, School of Medicine, Gyeongsang National University, Jinju, Republic of Korea
J Ethnopharmacol 139:605-15. 2012..Cinnamomum cassia Blume has been used as a traditional Chinese herbal medicine for alleviation of fever, inflammation, chronic bronchitis, and to improve blood circulation...Model-based approach to characterize efavirenz autoinduction and concurrent enzyme induction with carbamazepine
Min Zhu
Research and Development, Bristol Myers Squibb, P O Box 4000, Princeton, NJ 08543 4000, USA
Antimicrob Agents Chemother 53:2346-53. 2009Characterization of the time course and magnitude of enzyme induction due to multiple inducers is important for interpretation of clinical data from drug-drug interaction studies...Sulforaphane-stimulated phase II enzyme induction inhibits cytokine production by airway epithelial cells stimulated with diesel extract
Stacey A Ritz
Medical Sciences Division, Northern Ontario School of Medicine, East Campus Laurentian University, 935 Ramsey Lake Rd, Sudbury, ON P3E 2C6, Canada
Am J Physiol Lung Cell Mol Physiol 292:L33-9. 2007..Our studies show that sulforaphane can mitigate the effect of diesel in respiratory epithelial cells and demonstrate the chemopreventative potential of phase II enzyme enhancement...Diesel exhaust particles induce matrix metalloprotease-1 in human lung epithelial cells via a NADP(H) oxidase/NOX4 redox-dependent mechanism
Nadia Amara
Institut National de la Santé et de la Recherche Médicale U700, Paris, France
Am J Physiol Lung Cell Mol Physiol 293:L170-81. 2007..We conclude that alveolar alterations secondary to MMP-1 induction could explain lung function impairment associated with exposure to particulate pollution...The effects of cytochrome P450 induction by xenobiotics on endobiotic metabolism in pre-clinical safety studies
David E Amacher
Sciadvisor Toxicology Consultant, PO Box 254, Hadlyme, CT 06439, USA
Toxicol Mech Methods 20:159-66. 2010....The constitutive active/androstane receptor regulates phenytoin induction of Cyp2c29
Jonathan P Jackson
Laboratory of Pharmacology and Chemistry, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA
Mol Pharmacol 65:1397-404. 2004....Diallyl trisulfide inhibits phorbol ester-induced tumor promotion, activation of AP-1, and expression of COX-2 in mouse skin by blocking JNK and Akt signaling
Sangeeta Shrotriya
National Research Laboratory of Molecular Carcinogenesis and Chemoprevention, College of Pharmacy, Seoul National University, Seoul, South Korea
Cancer Res 70:1932-40. 2010..Taken together, the inhibitory effects of DATS on TPA-induced AP-1 activation and COX-2 expression through modulation of JNK or Akt signaling may partly account for its antitumor-promoting effect on mouse skin carcinogenesis...Selective inhibition of protein kinase C beta(2) attenuates inducible nitric oxide synthase-mediated cardiovascular abnormalities in streptozotocin-induced diabetic rats
Prabhakara Reddy Nagareddy
Faculty of Pharmaceutical Sciences, The University of British Columbia, British Columbia, Canada
Diabetes 58:2355-64. 2009....Antioxidant enzyme induction: a new protective approach against the adverse effects of diesel exhaust particles
Junxiang Wan
Hart and Louise Lyon Laboratory, Division of Clinical Immunology and Allergy, Department of Medicine, UCLA David Geffen School of Medicine, University of California, Los Angeles, California 90095 1690, USA
Inhal Toxicol 19:177-82. 2007..These findings suggest that overexpression of antioxidant enzymes could constitute a powerful potential chemopreventive approach against adverse effects induced by oxidant pollutants such as DEPs...New technologies and screening strategies for hepatotoxicity: use of in vitro models
Donna M Dambach
Discovery Toxicology, Bristol Myers Squibb Pharmaceutical Research Institute, Princeton, New Jersey 08543, USA
Toxicol Pathol 33:17-26. 2005....Dexamethasone induces pregnane X receptor and retinoid X receptor-alpha expression in human hepatocytes: synergistic increase of CYP3A4 induction by pregnane X receptor activators
J M Pascussi
Institut National de la Santé et de la Recherche Médicale U128, Institut Federatif de Recherche 24, Centre National de la Recherche Scientifique, Montpellier, France
Mol Pharmacol 58:361-72. 2000..These results reveal the existence of functional cross talk between the GR and PXR, and may explain some controversial aspects of the role of the GR in CYP3A4 induction...Cryopreserved primary hepatocytes as a constantly available in vitro model for the evaluation of human and animal drug metabolism and enzyme induction
J G Hengstler
Institute of Toxicology, Mainz, Germany
Drug Metab Rev 32:81-118. 2000The use of primary hepatocytes is now well established for both studies of drug metabolism and enzyme induction. Cryopreservation of primary hepatocytes decreases the need for fresh liver tissue...Antioxidant mechanism of heme oxygenase-1 involves an increase in superoxide dismutase and catalase in experimental diabetes
Saadet Turkseven
Department of Pharmacology, New York Medical College, Valhalla, NY 10595, USA
Am J Physiol Heart Circ Physiol 289:H701-7. 2005..These observations in experimental diabetes suggest that the vascular cytoprotective mechanism of HO-1 against oxidative stress requires an increase in EC-SOD and catalase...Induction of cyclooxygenase-2 by the activated MEKK1 --> SEK1/MKK4 --> p38 mitogen-activated protein kinase pathway
Z Guan
Department of Molecular Biology and Pharmacology and Medicine, Washington University School of Medicine, St Louis, Missouri 63110, USA
J Biol Chem 273:12901-8. 1998..Together, this data suggests a potential role for the MEKK1 --> SEK1/MKK4 --> p38 MAPK -->--> Cox-2 cascade linking members of the MAPK pathway with prostaglandin biosynthesis...SXR, a novel steroid and xenobiotic-sensing nuclear receptor
B Blumberg
Gene Expression Laboratory, The Salk Institute for Biological Studies, La Jolla, California 92037, USA
Genes Dev 12:3195-205. 1998..These results strongly support the steroid sensor hypothesis and suggest that broad specificity sensing receptors may represent a novel branch of the nuclear receptor superfamily...Role of aryl hydrocarbon receptor-mediated induction of the CYP1 enzymes in environmental toxicity and cancer
Daniel W Nebert
Department of Environmental Health and Center for Environmental Genetics, University of Cincinnati Medical Center, Cincinnati, Ohio 45267 0056, USA
J Biol Chem 279:23847-50. 2004..In the future, use of "humanized" mouse lines, containing a human AHR or CYP1 allele in place of the orthologous mouse gene, is one likely approach to show that the AHR and the CYP1 enzymes in human behave similarly to that in mouse...Inhibition of atypical PKC blocks ultraviolet-induced AP-1 activation by specifically inhibiting ERKs activation
C Huang
The Hormel Institute, University of Minnesota, Austin 55912, USA
Mol Carcinog 27:65-75. 2000..These results demonstrated that inhibition of aPKC impairs UV-induced AP-1 activation via suppression of ERKs activation but not of JNKs or p38 kinase activation...Comparison of activities dependent on glutathione S-transferase and cytochrome P-450 IA1 in cultured keratinocytes and reconstructed epidermal models
Ian R Harris
Paul Gerson Unna Skin Research Center, Beiersdorf AG, Hamburg, Germany
Skin Pharmacol Appl Skin Physiol 15:59-67. 2002..GST activity in models was equal or higher than the activity in epidermal samples. Reconstructed skin models may be useful to study the effects of non-water-soluble topical formulations on xenobiotic metabolism...Induction of heme oxygenase-1 and stimulation of cGMP production by hemin in aortic tissues from hypertensive rats
Joseph Fomusi Ndisang
Department of Physiology, University of Saskatchewan, Saskatoon, SK, Canada
Blood 101:3893-900. 2003..In adult SHRs, the HO/CO-sGC/cGMP system appeared normal, but desensitization of the sGC/cGMP pathway caused hypertension to prevail...Protein kinase C isoforms zeta and iota mediate collagenase expression and cartilage destruction via STAT3- and ERK-dependent c-fos induction
Gary J Litherland
Cell Signalling, Injury and Repair Group, Institute of Cellular Medicine, Newcastle University, Framlington Place, Newcastle upon Tyne NE2 4HH, United Kingdom
J Biol Chem 285:22414-25. 2010..aPKCs may constitute potential therapeutic targets for inflammatory joint diseases involving increased collagenase expression...Regulation of CYP2B6 in primary human hepatocytes by prototypical inducers
Stephanie R Faucette
Division of Drug Delivery and Disposition, School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599 7360, USA
Drug Metab Dispos 32:348-58. 2004..These results indicate that CYP2B6 is highly inducible by known CYP3A4 inducers and suggest that hPXR is a major determinant of CYP2B6-inducible expression for many, but not all, compounds evaluated in this study...Ah receptor in mice genetically "nonresponsive" for cytochrome P4501A1 induction: cytosolic Ah receptor, transformation to the nuclear binding state, and induction of aryl hydrocarbon hydroxylase by halogenated and nonhalogenated aromatic hydrocarbons in
P A Harper
Department of Pediatrics, Hospital for Sick Children, Toronto, Canada
Mol Pharmacol 40:818-26. 1991..The mechanistic reason for the diminished degree of difference between responsive and nonresponsive mice during embryonic cell culture (compared with adult tissues) is not yet known...The AH-receptor: genetics, structure and function
H I Swanson
Department of Pharmacology, Northwestern University Medical School, Chicago, IL 60611
Pharmacogenetics 3:213-30. 1993..The objectives of this review are to describe recent experimental results in this field and to use this information to develop a molecular model of AH-receptor mediated signal transduction...Induction of heme oxygenase 1 by nitrosative stress. A role for nitroxyl anion
Patrick Naughton
Vascular Biology Unit, Department of Surgical Research, Northwick Park Institute for Medical Research, Harrow, Middlesex HA1 3UJ, United Kingdom
J Biol Chem 277:40666-74. 2002..These findings indicate that heme oxygenase can act both as a sensor to and target of redox-based mechanisms involving NO and extend our knowledge on the biological function of HO-1 in response to nitrosative stress...Expression of interstitial collagenase during skeletal development of the mouse is restricted to osteoblast-like cells and hypertrophic chondrocytes
S Gack
Forschungszentrum Karlsruhe, Institut fur Genetik, Germany
Cell Growth Differ 6:759-67. 1995....Glioma cell extracellular matrix metalloproteinase inducer (EMMPRIN) (CD147) stimulates production of membrane-type matrix metalloproteinases and activated gelatinase A in co-cultures with brain-derived fibroblasts
T Sameshima
Department of Neurosurgery, Miyazaki Medical College, 5200 Kihara, Kiyotake, 889 1692, Miyazaki, Japan
Cancer Lett 157:177-84. 2000..Thus, we have shown, for the first time, that EMMPRIN causes increased expression of MT1-MMP and MT2-MMP, as well as increased production and activation of MMP-2...MAP kinase phosphatase 1: a novel mediator of biological effects of glucocorticoids?
A R Clark
Kennedy Institute of Rheumatology Division, Faculty of Medicine, Imperial College London, 1 Aspenlea Road, Hammersmith, London W6 8LH, United Kingdom
J Endocrinol 178:5-12. 2003..The potential relevance of MKP-1 to some of the biological effects of GCs is discussed...Pharmacokinetic drug interactions of gefitinib with rifampicin, itraconazole and metoprolol
Helen C Swaisland
AstraZeneca Pharmaceuticals, Macclesfield, UK
Clin Pharmacokinet 44:1067-81. 2005..Based on these findings, three clinical studies were carried out to investigate pharmacokinetic drug interactions in vivo with gefitinib...Regulation of CYP3A4 expression in human hepatocytes by pharmaceuticals and natural products
Judy L Raucy
California Toxicology Research Institute, Carlsbad, California 92009, USA
Drug Metab Dispos 31:533-9. 2003..Such results indicate that kava-kava required PXR to mediate CYP3A4 induction. Collectively, results demonstrated that several botancials induce CYP3A4, suggesting the potential for drug-herbal interactions...Role of Toll-like receptors 2 and 4 in the induction of cyclooxygenase-2 in vascular smooth muscle
Rosario Jimenez
Cardiothoracic Pharmacology, Unit of Critical Care Medicine, Royal Brompton Hospital, Faculty of Medicine, Imperial College, London SW3 6LY, UK
Proc Natl Acad Sci U S A 102:4637-42. 2005..These data have important implications for our understanding of the innate immune response in vascular cells and how it may impact vascular disease...Nitric oxide-mediated hyporeactivity to noradrenaline precedes the induction of nitric oxide synthase in endotoxin shock
C Szabo
William Harvey Research Institute, St Bartholomew s Hospital Medical College, London
Br J Pharmacol 108:786-92. 1993..The delayed hypotension and vascular hyporeactivity, however, is due to enhanced NO formation by the LPS-induced enzyme...The role of nuclear receptors in pharmacokinetic drug-drug interactions in oncology
S Harmsen
Utrecht University, Faculty of Science, Department of Pharmaceutical Sciences, Division of Biomedical Analysis, Sorbonnelaan 16, 3584 CA Utrecht, The Netherlands
Cancer Treat Rev 33:369-80. 2007..Understanding of the molecular mechanisms that underlie enzyme induction and the identification of (new) drugs involved in pharmacokinetic drug-drug interactions may contribute to ..Enzyme induction in cryopreserved human hepatocyte cultures
Sabine Kafert-Kasting
Cytonet GmbH and Co, KG Hannover Branch, Feodor Lynen Strasse 21, D 30625 Hannover, Germany
Toxicology 220:117-25. 2006..Nevertheless, enzyme induction factors caused by 24 h incubation with 50 microM rifampicin were similar in cryopreserved and non-frozen ..Cultures with cryopreserved hepatocytes: applicability for studies of enzyme induction
J G Hengstler
Institute of Toxicology, Mainz, Germany
Chem Biol Interact 125:51-73. 2000....Hepatocytes cultured in alginate microspheres: an optimized technique to study enzyme induction
M Ringel
Institute of Toxicology, University of Mainz, Germany
Toxicology 206:153-67. 2005..we optimized an in vitro system with hepatocytes cultured in alginate microspheres that allow studies of enzyme induction with excellent sensitivity...Metabolism-based drug-drug interactions: what determines individual variability in cytochrome P450 induction?
Cuyue Tang
Department of Drug Metabolism, Merck Research Laboratories, Sumneytown Pike, West Point, PA 19486 0004, USA
Drug Metab Dispos 33:603-13. 2005....Pharmacogenetics and enzyme induction/inhibition properties of antiepileptic drugs
Gail D Anderson
Department of Pharmacy, Box 357630, University of Washington, Seattle, WA 98195, USA
Neurology 63:S3-8. 2004..The decreased induction and inhibition effects and the lack of significant genetic polymorphism of the newer AEDs allow increased ease of use and perhaps greater safety, especially for patients taking multiple medications...Increased de novo purine synthesis by insulin through selective enzyme induction in primary cultured rat hepatocytes
M Tsuchiya
Division of Endocrinology and Metabolism, University of Tsukuba, Ibaraki, Japan
Am J Physiol 258:C841-8. 1990..b>Enzyme induction was supported by the results of kinetic analysis and the inhibition of the insulin-induced increase in enzyme ..Enzyme induction with antiepileptic drugs: cause for concern?
Martin J Brodie
Epilepsy Unit, Western Infirmary, Glasgow, United Kingdom
Epilepsia 54:11-27. 2013..Modern AEDs that do not possess this property have similar efficacy for the common epilepsies. Accordingly, perhaps consideration should be given to starting treatment with, or even switching patients to, non-enzyme-inducing AEDs...The use of human hepatocytes to investigate drug metabolism and CYP enzyme induction
Sylvie Klieber
Discovery Metabolism and Pharmacokinetics Safety, Sanofi Aventis Recherche, Montpellier, France
Methods Mol Biol 640:295-308. 2010..hepatocytes became the most predictive and widely used in vitro model for drug metabolism studies as well as enzyme induction. For this purpose, well-established and robust in vitro assays for the measurement of cell viability, ..Lack of effect of Ginkgo biloba on voriconazole pharmacokinetics in Chinese volunteers identified as CYP2C19 poor and extensive metabolizers
He Ping Lei
Institute of Clinical Pharmacology, Central South University, Changsha, Hunan, China
Ann Pharmacother 43:726-31. 2009..Because this enzyme exhibits genetic polymorphism, the inductive effect was expected to be modulated by the CYP2C19 metabolizer status...Genetics and physiology of proline utilization in Saccharomyces cerevisiae: enzyme induction by proline
M C Brandriss
J Bacteriol 140:498-503. 1979..The arginine-degradative pathway intersects the proline-degradative pathway at P5C. The P5C formed from the breakdown of arginine or ornithine can induce both proline-degradative enzymes by virtue of its conversion to proline...Cell-based high-throughput bioassays to assess induction and inhibition of CYP1A enzymes
Mei Fei Yueh
Puracyp Inc, Carlsbad, CA 92009, USA
Toxicol In Vitro 19:275-87. 2005..89 and 0.79 microM, respectively. In summary, chemicals that possess the ability to alter CYP1A expression or inhibit CYP1A enzyme activities can be rapidly identified with the cell-based bioassays described here...Contribution of UVB and UVA to UV-dependent stimulation of cyclooxygenase-2 expression in artificial epidermis
Andre Mahns
Institut fur Biochemie und Molekularbiologie I, Heinrich Heine Universitat Dusseldorf, 40225 Dusseldorf, Germany
Photochem Photobiol Sci 3:257-62. 2004..UV-induced COX-2 expression is not affected by inhibition of the MEK 1,2/ERK 1,2 pathways...Pyp1 and Pyp2 PTPases dephosphorylate an osmosensing MAP kinase controlling cell size at division in fission yeast
J B Millar
Division of Yeast Genetics, National Institute for Medical Research, Ridgeway, London, UK
Genes Dev 9:2117-30. 1995..We conclude that Pyp1 and Pyp2 are tyrosine-specific MAP kinase phosphatases that inactivate an osmoregulated MAP kinase, Sty1, which acts downstream of the Wis1 MAP kinase kinase to control cell size at division in fission yeast...Lansoprazole, a proton pump inhibitor, mediates anti-inflammatory effect in gastric mucosal cells through the induction of heme oxygenase-1 via activation of NF-E2-related factor 2 and oxidation of kelch-like ECH-associating protein 1
Tomohisa Takagi
Kyoto Prefectural University of Medicine, Japan
J Pharmacol Exp Ther 331:255-64. 2009..Phosphorylation of ERK and Nrf2, activation and nuclear translocation of Nrf2, and oxidation of Keap1 are all involved in the lansoprazole-induced HO-1 up-regulation...Oral exposure to benzo[a]pyrene in the mouse: detoxication by inducible cytochrome P450 is more important than metabolic activation
Shigeyuki Uno
Department of Environmental Health, Center for Environmental Genetics, University of Cincinnati Medical Center, OH 45267 0056, USA
Mol Pharmacol 65:1225-37. 2004....Hemin activation ameliorates HIV-1 infection via heme oxygenase-1 induction
Krishnakumar Devadas
Immunopathogenesis Section, Laboratory of Molecular Virology, Division of Emerging and Transfusion Transmitted Diseases, Center for Biologics Evaluation and Research, Food and Drug Administration, Rockville, MD 20852, USA
J Immunol 176:4252-7. 2006..These findings suggest an important role of hemin-induced HO-1 activity as a host defense mechanism against HIV-1 infection...The protective effects of oxyresveratrol imine derivative against hydrogen peroxide-induced cell death in PC12 cells
J Hur
Korea Food Research Institute, Seongnam, South Korea
Free Radic Res 47:212-8. 2013..Our results suggest that imine analogs of oxyresveratrol may be useful agents in reducing neuronal oxidative damage...Induction of cytochrome P4501A1
J P Whitlock
Department of Molecular Pharmacology, Stanford University School of Medicine, California 94305 5332, USA
Annu Rev Pharmacol Toxicol 39:103-25. 1999..b>Enzyme induction reflects increased transcription of the cognate CYP1A1 gene...Relative impact of genotype and enzyme induction on the metabolic capacity of CYP2C9 in healthy volunteers
S V Vormfelde
Department of Clinical Pharmacology, University Medical Center of the Georg August University Göttingen, Gottingen, Germany
Clin Pharmacol Ther 86:54-61. 2009Pharmacokinetics in individual subjects is determined by genes and environment. The relative contributions of enzyme induction and inherited genomic variation to cytochrome P450 enzyme 2C9 (CYP2C9) activity are unknown...Determination of cytochrome P450 1A2 and cytochrome P450 3A4 induction in cryopreserved human hepatocytes
Dirk Roymans
Preclinical Pharmacokinetics, Johnson and Johnson Pharmaceutical Research and Development, Turnhoutseweg 30, B 2340 Beerse, Belgium
Biochem Pharmacol 67:427-37. 2004..In conclusion, cryopreserved human hepatocytes may be a good alternative to fresh hepatocytes to study CYP1A and 3A induction...Cell-based models to study hepatic drug metabolism and enzyme induction in humans
Marc Vermeir
Johnson and Johnson Pharmaceutical Research and Development, Preclinical Pharmacokinetics, Turnhoutseweg 30, B 2340 Beerse, Belgium
Expert Opin Drug Metab Toxicol 1:75-90. 2005..The status of model development, their acceptance by health authorities and recommendations for the most appropriate use of the models are presented...Assessment of enzyme induction and aerenchyma formation as mechanisms for flooding tolerance in Trifolium subterraneum 'Park'
Samira Aschi-Smiti
Departement de Biologie, Faculte des Sciences de Tunis, 1060 Tunis, Tunisia
Ann Bot 91:195-204. 2003The objective of this study was to evaluate the role of enzyme induction and aerenchyma formation in prolonged tolerance to soil flooding in a variety of underground clover (Trifolium subterraneum 'Park') previously selected for ..[Effects of various ginkgo biloba extracts and proanthocyanidin on hepatic cytochrome P450 activity in rats]
Tomomi Sugiyama
National Institute of Health and Nutrition, Tokyo, Japan
Shokuhin Eiseigaku Zasshi 45:295-301. 2004..Further studies will be necessary to identify the constituent(s) of GBE involved in the induction of CYPs in vivo...Enzyme induction and inhibition by new antiepileptic drugs: a review of human studies
M S Benedetti
UCB Pharma, Nanterre, France
Fundam Clin Pharmacol 14:301-19. 2000..Gabapentin, vigabatrin and in particular levetiracetam appear to be devoid of significant enzyme inducing or inhibiting properties...Murine hepatoma (Hepa1c1c7) cells: a responsive in vitro system for chemoprotective enzyme induction by organoselenium compounds
Wael M El-Sayed
University of Utah, Department of Pharmacology and Toxicology, 30 South 2000 East, Room 201, Salt Lake City, UT 84112, USA
Toxicol In Vitro 21:157-64. 2007..Thus, Hepa1c1c7 cells appear to provide a viable platform for the study of protective enzyme regulation by selenocompounds, and with the exception of Ugt1a6, the mRNA elevations from selenazolidines are transcriptionally dependent...Cytochrome p450 turnover: regulation of synthesis and degradation, methods for determining rates, and implications for the prediction of drug interactions
Jiansong Yang
Simcyp Limited, Blades Enterprise Centre, John Street, Sheffield, UK
Curr Drug Metab 9:384-94. 2008..the accurate prediction of changes in drug concentration-time profiles associated with interactions involving enzyme induction and mechanism (time)-based inhibition (MBI)...Characterization of the induction of nitric oxide synthase and cyclo-oxygenase in rat aorta in organ culture
D Bishop Bailey
Department of Applied Pharmacology, National Heart and Lung Institute, Imperial College of Science and Technology, London
Br J Pharmacol 121:125-33. 1997..Also, unlike isolated cells in culture, the COX and NOS pathways were active independently; L-NAME had little effect on the activity of COX and indomethacin had little effect on the activity of NOS...Extrapolation of in vitro enzyme induction data to humans in vivo
G L Kedderis
Chemical Industry Institute of Toxicology, Research Triangle Park, NC 27709 2137, USA
Chem Biol Interact 107:109-21. 1997b>Enzyme induction generally increases the rate and extent of xenobiotic metabolism in vitro, but physiological constraints can dampen these effects in vivo...Enzyme inhibition and induction in liver disease
Pietro Palatini
Dipartimento di Farmacologia ed Anestesiologia, Universita di Padova, Largo E Meneghetti 2, 35131 Padova, Italy
Curr Clin Pharmacol 3:56-69. 2008....Enzyme induction and cytotoxicity in human hepatocytes by chlorpyrifos and N,N-diethyl-m-toluamide (DEET)
Parikshit C Das
Department of Environmental and Molecular Toxicology, North Carolina State University, Raleigh, NC 27695 7633, USA
Drug Metabol Drug Interact 23:237-60. 2008....Coordinated induction of drug transporters and phase I and II metabolism in human liver slices
P Olinga
Department of Pharmacokinetics and Drug Delivery, Groningen Research Institute for Pharmacy, University of Groningen, Ant Deusinglaan 1, 9713 AV Groningen, The Netherlands
Eur J Pharm Sci 33:380-9. 2008..The concomitant induction of metabolic enzymes and transporters shows that also in the human liver transporters and metabolic enzymes are regulated coordinately...Regulation of inducible AmpC beta-lactamase expression among Enterobacteriaceae
N D Hanson
Center for Research in Anti Infectives and Biotechnology, Departments of Pediatrics and Medical Microbiology and Immunology, Creighton University School of Medicine, Omaha, Nebraska 68178, USA
Curr Pharm Des 5:881-94. 1999..In doing so, the genes and gene products required for the process of AmpC induction are described. In addition, we review the data addressing cell wall recycling as it relates to AmpC induction...Peroxisome proliferator-activated receptor-gamma ligands induce heme oxygenase-1 in lung fibroblasts by a PPARgamma-independent, glutathione-dependent mechanism
Heather E Ferguson
Department of Environmental Medicine, University of Rochester, 601 Elmwood Ave, Box 692, Rochester, NY 14642, USA
Am J Physiol Lung Cell Mol Physiol 297:L912-9. 2009....Hydrogen peroxide is a second messenger in phase 2 enzyme induction by cancer chemopreventive dithiolethiones
Ryan Holland
Department of Chemistry and Biochemistry, University of Maryland, Baltimore County, 1000 Hilltop Circle, Baltimore, Maryland 21250, USA CA91032
Chem Res Toxicol 22:1427-34. 2009....Induction of drug metabolising enzymes: pharmacokinetic and toxicological consequences in humans
U Fuhr
Institute for Pharmacology, Clinical Pharmacology, University of Cologne, Germany
Clin Pharmacokinet 38:493-504. 2000..b>Enzyme induction has the net effect of increasing protein levels...Increased 6-hydroxycortisol excretion in pregnant women: implication of drug-metabolizing enzyme induction
C Ohkita
Department of Hospital Pharmacy, Tenri Hospital, Japan
DICP 24:814-6. 1990..081 +/- 0.031), 6-OHF values one week after delivery were significantly higher than those observed in the control group. These observations suggest that drug-metabolizing enzyme induction may occur during pregnancy.Simultaneous assessment of cytochrome P450 activity in cultured human hepatocytes for compound-mediated induction of CYP3A4, CYP2B6, and CYP1A2
Susan P Rhodes
Array BioPharma Inc, 3200 Walnut Street, Boulder, Colorado 80301, USA
J Pharmacol Toxicol Methods 63:223-6. 2011....Near completely humanized liver in mice shows human-type metabolic responses to drugs
Chise Tateno
Yoshizato Project, Cooperative Link of Unique Science and Technology for Economy Revitalization CLUSTER, Hiroshima, Japan
Am J Pathol 165:901-12. 2004..We conclude that the chimeric mouse developed in the present study is a useful model for assessing the functions and pharmacological responses of human hepatocytes...Induction of cytochrome P450s by terpene trilactones and flavonoids of the Ginkgo biloba extract EGb 761 in rats
Y Deng
Institute of Clinical Pharmacology, School of Pharmaceutical Sciences, Sun Yat Sen University, Guangzhou, China
Xenobiotica 38:465-81. 2008..Further study is needed to elucidate the mechanism of CYP3A induction by EGb 761 and bilobalide...Drug metabolizing enzyme induction pathways in experimental non-alcoholic steatohepatitis
Craig D Fisher
Department of Pharmacology and Toxicology, College of Pharmacy, University of Arizona, 1703 East Mabel, Tucson, AZ 85721, USA
Arch Toxicol 82:959-64. 2008..4) Hepatic Nqo1 mRNA levels were significantly increased by the MCD diet; however, additional induction of Nqo1 was still achievable following treatment with the Nrf2 activator OPZ...Effects of hepatic drug-metabolizing enzyme induction on clinical pathology parameters in animals and man
Daniela Ennulat
GlaxoSmithKline, King of Prussia, Pennsylvania 19406 0939, USA
Toxicol Pathol 38:810-28. 2010..Importantly, hepatic DME induction and associated changes in preclinical species are not necessarily predictive of the occurrence, magnitude, or enzyme induction profile in humans.CYP1A1 and CYP1A2 expression: comparing 'humanized' mouse lines and wild-type mice; comparing human and mouse hepatoma-derived cell lines
Shigeyuki Uno
Department of Biochemistry, Nihon University School of Medicine, 30 1 Oyaguchikami cho, Itabashi ku, Tokyo 173 8610, Japan
Toxicol Appl Pharmacol 237:119-26. 2009..These findings are relevant to risk assessment involving human CYP1A1 and CYP1A2 substrates, when administered to mice as environmental toxicants or drugs...
Research Grants
- Mitochondrial DNA Repair and BiogenesisRaquel R Bartz; Fiscal Year: 2013..the AMP-kinase pathway activation in sepsis as it relates to nuclear co-activator function and mtDNA repair enzyme induction. The completion of these Aims will improve our understanding of the role of mtDNA damage and repair in severe ..
- Isothiocyanate-Mediated Breast Cancer PreventionLouise R Howe; Fiscal Year: 2013..against rodent breast neoplasia induced by carcinogen treatment, most likely as a consequence of Phase II enzyme induction and resultant acceleration of carcinogen deactivation...
- In vivo effects of sulforaphane supplementation on normal human prostateDaniel W Lin; Fiscal Year: 2013..biopsy) and prostatectomy to assess carefully selected and evaluated measures of phase II detoxifying enzyme induction, intra-prostatic steroid hormone metabolism, oxidative damage, and growth of prostate cancer cells...
- Micro-Liver Platform Development for Evaluating Drug Disposition and Toxicity InSALMAN KHETANI; Fiscal Year: 2010..primary human hepatocytes are considered to be the gold standard for evaluating preclinical drug metabolism, enzyme induction, and liver-specific toxicity...
- NQO2: A novel target to reduce oxidative stress in retinal pigment epitheliumCHRISTOPHER KWAN HWANG; Fiscal Year: 2011..While some evidence suggests involvement of antioxidant enzyme induction, the mechanism of this protection is essentially unknown...
- PYRIDINE--ENZYME INDUCTION, METABOLISM, AND TOXICITYMelissa Runge Morris; Fiscal Year: 1991..These studies will form the basic for the overall objective of evaluating the effect of age, nutritional status, and biologic response modifiers on drug metabolism, induction and toxicity in extrahepatic tissues...
- CHRONOBIOLOGICAL INVESTIGATION OF TNF AND IL-2William Hrushesky; Fiscal Year: 1992..modulates glucocorticoid receptor binding, decreases available binding sites and reduces steroid-associated enzyme induction. These steroid/cytokine interactions suggest that chronobiologic investigation of cytokine toxicity and ..
- CHLOROANILINE-INDUCED NEPHROTOXICITYGARY RANKIN; Fiscal Year: 1992..The role of toxic metabolites will be investigated using enzyme induction and inhibition studies, glutathione depletion studies, quantitation of covalent binding of chloroanilines to ..
- ALKYLATING AGENTS AND DRUG RESISTANCEKenneth Tew; Fiscal Year: 1999..Using a battery of cDNA probes and isozyme specific antibodies, techniques will be applied which measure enzyme induction at both the mRNA and protein levels...
- ENZYME INDUCTION DEFECT--IMPLICATION FOR TOXICITYRobert Blouin; Fiscal Year: 1992..The specific aims of the project are: a) to investigate the enzyme induction defect in the fa/fa rodent, to determine if the defect is the result of an inheritable defect in the PB ..
- NOVEL CHARACTERISTICS OF 1-IMIDAZOLE ENZYME INDUCTIONMichael Franklin; Fiscal Year: 1990..The overall findings will provide greater accuracy to the prediction of drug-drug interactions likely to arise from the therapeutic use of N- substituted imidazoles...
- 1-Cys-peroxiredoxin, A Novel Lung Anti-oxidant EnzymeAron Fisher; Fiscal Year: 2004..To study tolerance in vivo, rats and mice will be exposed to hyperoxia; enzyme induction (mRNA, protein, activity) will be measured in control and selenium deficient rats exposed to 80 percent or ..
- REGULATION OF MUCOSAL IMMUNITY BY VITAMIN D3RAYMOND DAYNES; Fiscal Year: 2005..We will evaluate if such enzyme induction may represent a natural way to promote mucosal immunity to antigens delivered via the skin...
- INDUCTION OF AMINOLEVULINIC ACID SYNTHASE BY EXERCISEDavid Essig; Fiscal Year: 1993..Finally, we will isolate the gene for rat AS to eventually determine the sequence elements involved in AS enzyme induction. The results of this work may establish one of the pathways utilized by muscle cells to effect an overall ..
- STUDIES ON THE HALOGENATED AROMATIC HYDROCARBONSALAN POLAND; Fiscal Year: 1990..Several patterns of enzyme induction, i.e...
- EUCARYOTIC ENZYME INDUCTION: B-GALACTOSIDASE IN YEASTRobert Dickson; Fiscal Year: 1991..The information obtained from these studies will aid our understanding of more complex regulatory phenomena including cellular differentiation, environmental adaptation, and disease states such as cancer...
- ENVIRONMENTAL POLLUTANTS--THE INTESTINE AND NUTRITIONJAMES MANIS; Fiscal Year: 1980..Intestinal and hepatic enzyme induction will be measured as benzo(a)pyrene hydroxylase (aryl hydrocarbon hydroxylase) concurrently in order to ..
- NITRIC OXIDE & GUANYLATE CYCLASE IN LUNG CIRCULATIONDon Nakayama; Fiscal Year: 2000..The up regulation of iNOS and GTP-CH results from enzyme induction by inflammatory cytokines, principally TNFa and IFNg...
- PUTATIVE MEDIATORS OF INSULIN SECRETIONSUZANNE LAYCHOCK; Fiscal Year: 2000..adenosine monophosphate-mediated protein kinase (AMPK) and acetyl-CoA carboxylase activity, and antioxidant enzyme induction/activation...
- Dithiole thiones and ones--Chemistry to BiochemistryJAMES FISHBEIN; Fiscal Year: 2005..However, a major area of uncertainty is the molecular nature of the initiation steps involved in Phase 2 enzyme induction. As elaborated in this proposal, this is in part due to the dearth of information regarding the chemistry and ..
- PRIMATE ENDOCRINE REGULATION IN THE PERINATAL PERIODRobert Jaffe; Fiscal Year: 2003..adrenal gland is to cardinal importance because of 1) the pivotal role adrenal corticosteroids play in early enzyme induction, the coordinate development of independent organ systems necessary or intrauterine homeostasis and ..
- Mechanism of Anticarcinigenic Effects of MyristicinHASSAN AHMAD; Fiscal Year: 2004..The results are expected to help us understand the Phase-II enzyme induction by myristicin and its potential in developing pharmacologically effective dietary strategies for cancer ..
- TOXICITY OF PURE PCBS FOR RHESUS MONKEYSWILBUR MC NULTY; Fiscal Year: 1980..and the kinetics of storage of parent compound in fat and liver and the pattern of hepatic microsomal enzyme induction will be determined for each isomer...
- Oxidation Hypothesis--Paradoxes and PitfallsSampath Parthasarathy; Fiscal Year: 2006..we propose that "oxidative stress in plasma might result in an elevated tissue (arterial) antioxidant enzyme induction and, in addition, such oxidative stress might itself could lead to lower plasma cholesterol levels...
- INTERACTIONS OF L-ACETYLMETHADOL WITH METHADONEFRANCIS TSE; Fiscal Year: 1980..Incidence of drug metabolizing enzyme induction or inhibition will be investigated, and the effect of these changes on the distribution and elimination of ..
- AMINO ACID REGULATORY INTERACTIONS IN YEASTRichard Weiss; Fiscal Year: 1980..The kinetics of enzyme induction and repression will be compared to that observed when arginine is added to the growth medium...
- CONTROL OF GENE EXPRESSION BY DIOXINJames Whitlock; Fiscal Year: 2001..In humans, TCDD produces adaptive and adverse effects (enzyme induction, chloracne); however, the risk that TCDD poses to public health is a matter of current debate...
- Novel Transcription Profiling in Toxicologic AssaysMary Warren; Fiscal Year: 2005..This is due to the many adverse drug reactions and drug-drug interactions that result from drug metabolism, enzyme induction or inhibition of drug metabolizing enzymes...
- ANTICONVULSANT, DRUG-INDUCED MINERAL DISORDERSTHEODORE HAHN; Fiscal Year: 1980..Finally, studies of drug effects on in vitro hepatic vitamin D metabolism will further define the role of microsomal enzyme induction in this disorder.
- ETHANOL EFFECTS ON BONE FORMATION IN PREGNANCYMartin Ronis; Fiscal Year: 2006..The role of CYP2E1 and free radicals in the skeletal toxicity of ethanol during these periods will also be studied. ..
- ETHANOL METABOLISM IN PREGNANCY--ROLE OF DIETMartin Ronis; Fiscal Year: 2005....
- Novel noninvasive assessment of cytochrome P450 activityEvan Kharasch; Fiscal Year: 2009..This approach may identify inter-individual variability in drug disposition and response;permit more individualized dosing, and reduces the cost of drug interaction studies. ..
- Androgenic And Antiandorgenic Interactions Of PC-SPESCHARLES ROSELLI; Fiscal Year: 2002..Specific Aim 3: To evaluate the effect of PCSPES on Cytochrome P450-mediated metabolism of androgenic and antiandrogenic drugs by the liver, in order to identify possible interactions of PC-SPES with other hormone therapies. ..
- RECEPTOR MEDIATED OXIDATIVE STRESSHOWARD SHERTZER; Fiscal Year: 2003..These studies will improve our understanding of how PHAHs such as TCDD generate oxidative stress and mutagenesis, leading to better models for risk assessment and novel strategies for intervention in PHAH-mediated toxicity. ..
- Glutathione in Environmental Toxicity and DiseaseHOWARD SHERTZER; Fiscal Year: 2007..Our proposed research should therefore help focus future genotype-phenotype association studies between the appropriate DNA variant sites in the GCLC and GCLM genes and disease. ..
- Mechanisms of Myocardial Radiofrequency Scar ExpansionRupak Mukherjee; Fiscal Year: 2004..abstract_text> ..
- ANESTHETIC RENAL METABOLISM--MECHANISMS AND CONSEQUENCESEvan Kharasch; Fiscal Year: 2002..More broadly, resulting biochemical and clinical insights will be applicable to the numerous other nephrotoxic haloalkenes that are ubiquitous environmental contaminants. ..
- ENHANCED APOPTOSIS BY TARGETING PROTEIN REDOX STATUSMohan Natarajan; Fiscal Year: 2009..abstract_text> ..
- CELL-SELECTIVE EXPRESSION OF FIBROTIC GENE PATHWAYSNestor Gonzalez Cadavid; Fiscal Year: 2008..We expect that our studies would lead to the detection of novel targets of antifibrotic therapy for penile and vascular diseases of considerable public health impact. [unreadable] [unreadable] [unreadable]..
- ARGINASE AND ARTERIAL INJURYWilliam Durante; Fiscal Year: 2009....
- Fibronectin Fragment-Induced Osteolysis Mediated by MMPsSunil Kapila; Fiscal Year: 2009..These studies will provide a fundamental understanding of the basis for bone loss in periodontal disease and other osteolytic diseases. ..
- Coordinate Regulation of Uptake and Efflux TransportersCurtis D Klaassen; Fiscal Year: 2010....
- Molecular mechanisms of synapse lose by polo kinasesDaniel T Pak; Fiscal Year: 2010..abstract_text> ..
- Hepatic Steatosis Modulation by Apo B Gene TranscriptionJANET DEHOFF SPARKS; Fiscal Year: 2010....
- Feedback and Hormonal Regulation of Hepatic HMG-CoA ReductaseGENE CHARLES NESS; Fiscal Year: 2010....
- Clinical and Molecular Evaluation of Cancer Therapy Induced MucositisSharon Gordon; Fiscal Year: 2007..Demonstration of safety and tolerability will provide a basis to test further this route of administration. Hence, this proposal holds promise for clinical application in a relatively short period. [unreadable] [unreadable]..
- CYTOKINE DYSFUNCTION AND LUNG 5LO METABOLISM IN AIDSMichael Coffey; Fiscal Year: 2002..This proposal will further enhance our ability to correct this defect and help boost AM, PBM, and PMN defenses against opportunistic infections in the lung in HIV disease. ..
- Pharmacogenetics of MethadoneC Devane; Fiscal Year: 2003..This study will form the basis for subsequent studies which should provide a more rational basis for dosing of methadone in pregnant addicts. ..
- MAP KINASE REGULATION OF MICROGLIAL ACTIVATIONNarayan Bhat; Fiscal Year: 2004..The suppressive effects of the kinase inhibitors on activation-associated microglial functions; i.e., targeting of oligodendrocytes and myelin phagocytosis will be tested using in vitro models. ..
- Prostate Cancer: A Mouse Model Testing 15-Lipoxygenase-1Uddhav Kelavkar; Fiscal Year: 2004..abstract_text> ..
- CYP1A1 GENE AND ENVIRONMENTAL TOXICITYDaniel Nebert; Fiscal Year: 2005..abstract_text> ..
- IVIVC MODEL FOR RENAL DRUG CLEARANCEThomas Dowling; Fiscal Year: 2005..abstract_text> ..
- Validation of rat models for resistant epilepsy therapyWolfgang Loscher; Fiscal Year: 2005..Our goal is to establish standard assays that can be employed by researchers to continue the search for treatments of drug resistant epilepsy. ..
- ADVANCES IN SELENIUM SUPPLEMENTATIONMichael Franklin; Fiscal Year: 2006..abstract_text> ..
- Gene Targets of Wnt Signaling in Pancreatic CancerAndrew Lowy; Fiscal Year: 2006..Our long-range goal is to understand how these genes contribute to pancreatic carcinogenesis with the hope that they can be modulated for therapeutic purposes. ..
- Selective Induction of Estrogen Conjugative MetabolismBao Ting Zhu; Fiscal Year: 2006..These studies will also provide examinations of the important roles of bioactive estrogen metabolites (e.g., 4-OH-E2 and 16alpha-OH-E2) in estrogen-induced cancers. ..
- Nitric oxide synthase 3 and left ventricular remodelingKENNETH BLOCH; Fiscal Year: 2006..Improved understanding of the role of NOS3 in ventricular remodeling may lead to the development of novel therapeutic approaches to preventing congestive heart failure and its associated morbidity and mortality after MI. ..
- Effects of ethanol and CYP2E1 on liver functionArthur Cederbaum; Fiscal Year: 2007..unreadable] [unreadable] [unreadable] [unreadable]..
- HIGH RESOLUTION ECHOCARDIOGRAPHY SYSTEMMichael Zile; Fiscal Year: 2001..This will foster interdisciplinary investigation, support NIH-funded investigators and trainees, and enhance the competitiveness of MUSC investigators. ..