Document Detail


Noninvolvement of CYP2E1 in the (omega-1)-hydroxylation of fatty acids in rat kidney microsomes.
MedLine Citation:
PMID:  9354595     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Y Amet; A Zerilli; T Goasduff; Y Dréano; F Berthou
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Biochemical pharmacology     Volume:  54     ISSN:  0006-2952     ISO Abbreviation:  Biochem. Pharmacol.     Publication Date:  1997 Oct 
Date Detail:
Created Date:  1997-11-21     Completed Date:  1997-11-21     Revised Date:  2003-11-14    
Medline Journal Info:
Nlm Unique ID:  0101032     Medline TA:  Biochem Pharmacol     Country:  ENGLAND    
Other Details:
Languages:  eng     Pagination:  947-52     Citation Subset:  IM    
Affiliation:
Laboratoire de Biochimie-Nutrition, Faculté de Médecine, Brest, France. Yolande.Amet-LeBloas@univ-brest.fr
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MeSH Terms
Descriptor/Qualifier:
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:
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

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