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KMID : 0617219930040010030
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Duksung Bulletin Phamaceutical Sciences
1993 Volume.4 No. 1 p.30 ~ p.35
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INDUTION OF CYP2E1 BY ORGANIC SOLVENTS
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Abstract
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Pyridine and acetone are efficacious inducers of CYP2E1 in both rats and rabbits. The response in the elevation of CYP2E1 levels, changes in CYP2E1 mRNA levels, and enhanced translational processing of hepatic CYP2E1 mRNA during the early phase of CYP2E1 induction by the solvents pyridine and acetone were examined. Time-dependent increase in CYP2E1 levels occurred at early times (6-24h) following a single dose of pyridine treatment, as assessed by Western immunoblot analysis, whereas the levels in CYP2E1 mRNA transiently decreased at 12 h post-treatment, returning to the level present in untreated animals. Autoradiographic analysis of [^14C]leucine-labeled microsomal proteins isolated at 6 h from the animals treated with the solvent showed an enhanced intensity of a band migrating in the region of CYP2E1, relative to control. The effects of pyridine on the distribution of CYP2E1 polysomal mRNA was examined to determine whether increased ribosomal loading on CYP2E1 mRNA is associated with the rapid induction of CYP2E1 protein. Northern and slot blot analyses of fractions from the cytoplasmic extracts using a CYP2E1-specific oligonucleotide probe revealed a shift in distribution of CYP2E1 message from monoribosomal fractions towards the heavier polyribosomal fractions following the solvent treatment, providing evidence that induction of CYP2E1 at early times following pyridine treatment involves enhanced translational efficiency through increased loading of ribosomes on CYP2E1 mRNA. These results suggest that induction of CYP2E1 occurs through an enhanced rate of protein synthesis in the absence of transcriptional activation.
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