Ethanol induction of CYP2A5: role of CYP2E1-ROS-Nrf2 pathway.

Toxicological Sciences : an Official Journal of the Society of Toxicology
Yongke LuA I Cederbaum

Abstract

Chronic ethanol consumption was previously shown to induce CYP2A5 in mice, and this induction of CYP2A5 by ethanol was CYP2E1 dependent. In this study, the mechanisms of CYP2E1-dependent ethanol induction of CYP2A5 were investigated. CYP2E1 was induced by chronic ethanol consumption to the same degree in wild-type (WT) mice and CYP2A5 knockout (Cyp2a5 (-/-)) mice, suggesting that unlike the CYP2E1-dependent ethanol induction of CYP2A5, ethanol induction of CYP2E1 is not CYP2A5 dependent. Microsomal ethanol oxidation was about 25% lower in Cyp2a5 (-/-) mice compared with that in WT mice, suggesting that CYP2A5 can oxidize ethanol although to a lesser extent than CYP2E1 does. CYP2A5 was induced by short-term ethanol consumption in human CYP2E1 transgenic knockin (Cyp2e1 (-/-) KI) mice but not in CYP2E1 knockout (Cyp2e1 (-/-)) mice. The redox-sensitive transcription factor nuclear factor-erythroid 2-related factor 2 (Nrf2) was also induced by acute ethanol in Cyp2e1 (-/-) KI mice but not in Cyp2e1 (-/-) mice. Ethanol induction of CYP2A5 in Nrf2 knockout (Nrf2 (-/-)) mice was lower compared with that in WT mice, whereas CYP2E1 induction by ethanol was comparable in WT and Nrf2 (-/-) mice. Antioxidants (N-acetyl-cysteine...Continue Reading

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Citations

Sep 14, 2015·Naunyn-Schmiedeberg's Archives of Pharmacology·Feng HongYongke Lu
Nov 28, 2015·Journal of Extracellular Vesicles·Xiaoying ZhuangHuang-Ge Zhang
Jun 27, 2013·Free Radical Research·B SidP B Calderon
Mar 20, 2015·The American Journal of Chinese Medicine·Meng WangXiaoying Zhang
Dec 9, 2014·Autophagy·Jia Luo
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Apr 25, 2016·Drug and Alcohol Dependence·Noah R GubnerMaciej L Goniewicz
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Mar 24, 2018·International Journal of Obesity : Journal of the International Association for the Study of Obesity·Kesheng WangYongke Lu
Dec 19, 2017·Evidence-based Complementary and Alternative Medicine : ECAM·Qiong-Hui HuangYou-Liang Xie
Oct 4, 2014·World Journal of Gastroenterology : WJG·Wei TangMamadou Diallo
Feb 2, 2018·Nihon eiseigaku zasshi. Japanese journal of hygiene·Akiko Matsumoto
Feb 5, 2015·Medical Science Monitor : International Medical Journal of Experimental and Clinical Research·Rui HeJinguang Ruan
Sep 3, 2020·American Journal of Physiology. Gastrointestinal and Liver Physiology·Xue ChenYongke Lu
Apr 24, 2021·Free Radical Biology & Medicine·Xue ChenYongke Lu
Oct 11, 2021·Cell Death and Differentiation·Timothy J HumptonKaren H Vousden

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