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논문 기본 정보
- 자료유형
- 학술저널
- 저자정보
- 발행연도
- 2016.1
- 수록면
- 173 - 178 (6page)
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Liver cells experience hypoxic stress when drug-metabolizing enzymes excessively consume O2 for hydroxylation. Hypoxic stress changes the transcription of several genes by activating a heterodimeric transcription factor called hypoxia-inducible factor- 1α/β (HIF-1α/β). We found that hypoxic stress (0.1% O2) decreased the expression of cytochrome P450 7A1 (CYP7A1), a rate-limiting enzyme involved in bile acid biosynthesis.
Chenodeoxycholic acid (CDCA), a major component of bile acids, represses CYP7A1 by activating a transcriptional repressor named small heterodimer partner (SHP). We observed that hypoxia decreased the levels of both CDCA and SHP, suggesting that hypoxia repressed CYP7A1 without inducing SHP. The finding that overexpression of HIF-1α increased the activity of the CYP7A1 promoter suggested that hypoxia decreased the expression of CYP7A1 in a HIF-1-independent manner. Thus, the results of this study suggested that hypoxia decreased the activity of CYP7A1 by limiting its substrate O2, and by decreasing the transcription of CYP7A1.
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참고문헌 (26)
참고문헌 신청
Nath B / 2012 / Hypoxia, hypoxia inducible factors: diverse roles in liver diseases / Hepatology 55:622~633
Jungermann K / 2000 / Oxygen : modulator of metabolic zonation, disease of the liver / Hepatology 31:255~260
Arteel GE / 1997 / Chronic enteral ethanol treatment causes hypoxia in rat liver tissue in vivo / Hepatology 25:920~926
Masson N / 2003 / HIF prolyl, asparaginyl hydroxylases in the biological response to intracellular O(2)levels / J Cell Sci 116:3041~3049
Bruick RK / 2001 / A conserved family of prolyl-4-hydroxylases that modify HIF / Science 294:1337~1340
Jungermann K / 2000 / Oxygen : modulator of metabolic zonation, disease of the liver / Hepatology 31:255~260
Arteel GE / 1997 / Chronic enteral ethanol treatment causes hypoxia in rat liver tissue in vivo / Hepatology 25:920~926
Masson N / 2003 / HIF prolyl, asparaginyl hydroxylases in the biological response to intracellular O(2)levels / J Cell Sci 116:3041~3049
Bruick RK / 2001 / A conserved family of prolyl-4-hydroxylases that modify HIF / Science 294:1337~1340
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