| Noninvolvement of CYP2E1 in the (omega-1)-hydroxylation of fatty acids in rat kidney microsomes. | |
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MedLine Citation:
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PMID: 9354595 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Pyrazole, acetone, and ethanol are known to induce cytochrome P450 2E1 (CYP2E1) and fatty acid (omega-1)-hydroxylation in rat liver microsomes. However, the nature of the P450 enzyme involved in this (omega-1)-hydroxylation has not been clearly established in extrahepatic tissues such as kidney. Four enzymatic activities (hydroxylations of chlorzoxazone, 4-nitrophenol, and two fatty acids) were assayed in kidney microsomal preparations of rats treated with CYP2E1 inducers. Per os treatment resulted in large increases (threefold to fivefold) in the chlorzoxazone and 4-nitrophenol hydroxylations, and up to a ninefold increase when ethanol was administered by inhalation. However, neither the omega-hydroxylation nor the (omega-1)-hydroxylation of fatty acids was modified. Immunoinhibition specific to CYP2E1 did not significantly decrease the omega and (omega-1)-lauric acid hydroxylations, while the polyclonal anti-CYP4A1 antibody inhibited in part both the omega- and (omega-1)-hydroxylations. Chemical inhibitions using either CYP2E1 competitive inhibitors (such as chlorzoxazone, DMSO, and ethanol) or P450 mechanism-based inhibitors (such as diethyldithiocarbamate and 17-octadecynoic acid) led to a partial inhibition of the hydroxylations. All these results suggest that fatty acid (omega-1)-hydroxylation, a highly specific probe for CYP2E1 in rat and human liver microsomes, is not mediated by CYP2E1 in rat kidney microsomes. In contrast to liver, where two different P450 enzymes are involved in fatty acid omega- and (omega-1)-hydroxylations, the same P450 enzyme, mainly a member of the CYP4A family, was involved in both hydroxylations in rat renal microsomes. |
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Authors:
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Y Amet; A Zerilli; T Goasduff; Y Dréano; F Berthou |
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Publication Detail:
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Type: Journal Article |
Journal Detail:
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Title: Biochemical pharmacology Volume: 54 ISSN: 0006-2952 ISO Abbreviation: Biochem. Pharmacol. Publication Date: 1997 Oct |
Date Detail:
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Created Date: 1997-11-21 Completed Date: 1997-11-21 Revised Date: 2003-11-14 |
Medline Journal Info:
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Nlm Unique ID: 0101032 Medline TA: Biochem Pharmacol Country: ENGLAND |
Other Details:
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Languages: eng Pagination: 947-52 Citation Subset: IM |
Affiliation:
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Laboratoire de Biochimie-Nutrition, Faculté de Médecine, Brest, France. Yolande.Amet-LeBloas@univ-brest.fr |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Alkane 1-Monooxygenase Animals Chlorzoxazone / metabolism Cytochrome P-450 CYP2E1 / antagonists & inhibitors, immunology, metabolism* Cytochrome P-450 Enzyme System / metabolism* Enzyme Inhibitors / immunology, pharmacology Fatty Acids / metabolism* Immunologic Techniques Kidney / enzymology* Male Microsomes / enzymology Mixed Function Oxygenases / metabolism* Nitrophenols / metabolism Rats Rats, Sprague-Dawley |
| Chemical | |
Reg. No./Substance:
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0/Enzyme Inhibitors; 0/Fatty Acids; 0/Nitrophenols; 100-02-7/4-nitrophenol; 9035-51-2/Cytochrome P-450 Enzyme System; 95-25-0/Chlorzoxazone; EC 1.-/Mixed Function Oxygenases; EC 1.14.14.1/Cytochrome P-450 CYP2E1; EC 1.14.15.3/Alkane 1-Monooxygenase |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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