Molecular cloning and sequence analysis of hamster CYP2E1

Sakuma, Tsutomu; Takai, Miwa; Yokoi, Tsuyoshi; Kamataki, Tetsuya

doi:10.1016/0167-4781(94)90043-4

Cited by 6 publications

(2 citation statements)

References 8 publications

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“…Till now, several genes of P450 isozymes of hamsters have been cloned and their analogies to those of other animals have been discussed [18,40,44,[61][62][63][64], but little is known about the mechanisms involved in the responsiveness of hamster P450 isotypes to endogenous compounds and chemical inducers or suppressors [4,41,65]. Further characterization of hamster P450 isozymes would help in understanding the system of regulation of P450 in this valuable laboratory animal.…”

Section: Discussionmentioning

confidence: 99%

The effects of diabetes with hyperlipidemia on P450 expression in APA hamster livers

Takatori

Akahori

Kawamura

et al. 2002

J Biochem & Molecular Tox

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The effect of chronic hyperglycemia and hyperlipidemia induced by streptozotocin (SZ) on the expression of P450 in the liver of APA hamsters was studied in this experiment. No effect on the total activity of P450 was seen in SZ-induced diabetic hamsters throughout the experimental period. At 1 and 6 months after SZ-injection, the levels of CYP1A, 2C6, and 3A of SZ-injected hamsters were much lower than those of age-matched control hamsters. CYP2B expression tended to decrease and CYP2E1 and 4A expression tended to increase in SZ-injected hamsters, although the results were not significant. At 3 months after SZ-injection, however, no significant difference between SZ-injected and normal hamsters was seen in these P450 isozymes. On the other hand, CYP2C11 expression was slightly depressed in SZ1M and SZ6M, and almost equivalent to control hamsters in SZ3M. Immunohistochemistry by the use of each isozyme antibody revealed that SZ-induced diabetes affected the localization of CYP2C6, 3A, and 4A in the hepatic acinus. The expression of CYP2C6 and 3A was depressed mainly in the periportal region of the acinus, and CYP4A expression was induced mainly in the perivenous region by SZ-induced diabetes. On the other hand, the expression pattern of CYP1A, 2B, 2C11, and 2E1 were not affected. These results demonstrate that the effects of SZ-induced diabetes on hepatic P450 differ for each isozyme in APA hamsters and also differ from those of other experimental diabetic animals, including golden hamsters.

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Section: Discussionmentioning

confidence: 99%

The effects of diabetes with hyperlipidemia on P450 expression in APA hamster livers

Takatori

Akahori

Kawamura

et al. 2002

J Biochem & Molecular Tox

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show abstract

“…Recently some P450 isozymes of hamsters have been characterized and compared to those of other laboratory animals [20][21][22][23][24], but as yet no detailed information on the characteristics of the hamster P450 system is available. In this study, we examined age-related changes and expression patterns of hamster P450 isozymes in the liver by immunohistochemical analysis and western blot analysis.…”

Section: Introductionmentioning

confidence: 99%

Localization and Age-Related Changes in Cytochrome P450 Expression in APA Hamster Livers.

Takatori

Akahori²,

Kawamura

et al. 2000

Exp. Anim.

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Abstract:To establish the baseline data, age-related changes and the regional expression of the hepatic P450 isozymes in Syrian hamsters of the APA strain at 3, 6, 12, 18 months old were examined by immunological techniques. Immunohistochemical analysis of liver serial sections revealed that the midzonal and perivenous regions (zones 2 and 3, respectively) were stained with the anti-rat CYP1A1/2, 2B1/2 and 2E1 antibodies. These three antibodies most intensely stained the hepatocytes around the central vein. An anti-rat CYP3A2 staining section had a staining pattern with equally intense reactions in zones 2 and 3. On the other hand, CYP2C6, 2C11 and 4A1 were distributed diffusely throughout the hepatic acinus. There was no age-related difference in the expression pattern of any of the P450 isozymes examined. Total P450 content had a peak at 6 months of age and decreased to 60% of that level thereafter. Western-blot analysis revealed that the peak expressions of the isozymes detected with anti-rat CYP1A1/2, 2C6, 2E1 and 3A2 antibodies were observed in 6-month-old hamsters and declined in older ones. The CYP2B and 2C11 content reached the maximum at the age of 6 months and maintained almost the same level thereafter. The CYP4A level did not change from 3 to 6 months, and then declined to about 40% of the younger level at 12 and 18 months of age. These results suggest that the hepatic P450 isozymes of APA hamsters have region-specific expressions and most isozymes have their peaks of expression at 6 months of age, which differs from the patterns for rat P450.

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Induction of cytochromes P450 1A, 2B and 2E in hamster tissues by acetone

Chen

Ueng

1997

Archives of Toxicology

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The inductive effects of acetone on cytochromes P450 1A, 2B and 2E in liver, kidney and lung were studied using hamsters administered acetone in drinking water. Acetone administration caused five-, two- and sixfold increases of the activities of aniline hydroxylase, ethoxyresorufin O-dealkylase and pentoxyresorufin O-dealkylase in liver microsomes; eight- and twofold increases of aniline hydroxylation and ethoxyresorufin O-dealkylation in kidney; and a twofold increase of aniline hydroxylation in lung, respectively. Immunoblot analyses of microsomal proteins using mouse monoclonal antibody 1-12-3 to rat P450 1A1 and rabbit antibody to human P450 2E1 revealed that acetone resulted in about three-, four- and twofold increases of proteins immunorelated to P450s 1A and 2E in hamster liver, kidney, and lung, respectively. Protein blot analysis using mouse monoclonal antibody 2-66-3 to rat P450 2B1 showed that acetone caused five- and twofold increases, respectively, of an immunoreactive protein in hamster liver and kidney but decreased the P450 2B protein by 48% in lung. RNA blot analyses using cDNA probes derived from mouse P450 1A1 and rat P450 2B1 cDNA clones demonstrated that acetone elicited two- and twelvefold increases of the mRNA levels of P450s 1A and 2B in hamster liver, respectively. Northern blot analyses using oligonucleotide probes derived from hamster P450 2E1 cDNA sequence detected two species of hybridizable mRNA in control liver. Acetone preferentially caused a threefold increase in the level of the larger-sized mRNA. Acetone produced little increase or no effect on mRNAs of cytochromes P450 1A, 2B and 2E in kidney and lung. The present study demonstrates that acetone induces the catalytic activity, protein and mRNA levels of P450s 1A, 2B and 2E in hamster liver, and causes various changes of the P450 levels in kidney and lung. Acetone induction of hamster P450s 1A, 2B and 2E might involve transcriptional and post-transcriptional mechanisms.

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Molecular cloning and sequence analysis of hamster CYP2E1

Cited by 6 publications

References 8 publications

The effects of diabetes with hyperlipidemia on P450 expression in APA hamster livers

The effects of diabetes with hyperlipidemia on P450 expression in APA hamster livers

Localization and Age-Related Changes in Cytochrome P450 Expression in APA Hamster Livers.

Induction of cytochromes P450 1A, 2B and 2E in hamster tissues by acetone

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