Bidirectional Regulation of NAD(P)H Quinone Dehydrogenase 1 Expression in Mouse Hepatic Stellate Cells- Acute versus Long-Term Ethanol Exposure
Main Article Content
Abstract
Conclusions: Our findings suggest that ethanol upregulates NQO1 expression by activating the AhR-Nrf2 pathway. Long-term ethanol exposure sustains low level of AhR protein and diminishes the inducibility of its target genes Nrf2 and NQO1 by BaP. These findings will contribute to understanding the synergistic toxicity of ethanol and polycyclic aromatic hydrocarbon compounds, such as BaP.
Keywords:
ethanol, benzo(a)pyrene, aryl hydrocarbon receptor, nuclear factor erythroid 2-related factor-2, NAD(P)H quinone dehydrogenase 1
Article Details
How to Cite
YANG, Hong; ZHANG, Ningya; GUO, ZhongMao.
Bidirectional Regulation of NAD(P)H Quinone Dehydrogenase 1 Expression in Mouse Hepatic Stellate Cells- Acute versus Long-Term Ethanol Exposure.
Medical Research Archives, [S.l.], v. 11, n. 2, feb. 2023.
ISSN 2375-1924.
Available at: <https://esmed.org/MRA/mra/article/view/3586>. Date accessed: 14 may 2025.
doi: https://doi.org/10.18103/mra.v11i2.3586.
Section
Research Articles
The Medical Research Archives grants authors the right to publish and reproduce the unrevised contribution in whole or in part at any time and in any form for any scholarly non-commercial purpose with the condition that all publications of the contribution include a full citation to the journal as published by the Medical Research Archives.
References
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32. He F, Ru X and Wen T. NRF2, a Transcription Factor for Stress Response and Beyond. Int J Mol Sci. 2020;21.
33. Hankinson O. The aryl hydrocarbon receptor complex. Annu Rev Pharmacol Toxicol. 1995;35:307-340.
34. Nebert DW and Karp CL. Endogenous functions of the aryl hydrocarbon receptor (AHR): intersection of cytochrome P450 1 (CYP1)-metabolized eicosanoids and AHR biology. J Biol Chem. 2008;283:36061-36065.
35. Abbott BD, Perdew GH and Birnbaum LS. Ah receptor in embryonic mouse palate and effects of TCDD on receptor expression. Toxicol Appl Pharmacol. 1994;126:16-25.
36. Wang Z, Yang H, Ramesh A, Roberts LJ, Zhou L, Lin X, Zhao Y and Guo Z. Overexpression of Cu/Zn-superoxide dismutase and/or catalase accelerates benzo(a)pyrene detoxification by upregulation of the aryl hydrocarbon receptor in mouse endothelial cells. Free Radic Biol Med. 2009;47:1221-1229.
37. Ross D and Siegel D. The diverse functionality of NQO1 and its roles in redox control. Redox Biol. 2021;41:101950.
38. Barnes SL, Singletary KW and Frey R. Ethanol and acetaldehyde enhance benzo[a]pyrene-DNA adduct formation in human mammary epithelial cells. Carcinogenesis. 2000;21:2123-2128.
39. Ahrendt SA, Chow JT, Yang SC, Wu L, Zhang MJ, Jen J and Sidransky D. Alcohol consumption and cigarette smoking increase the frequency of p53 mutations in non-small cell lung cancer. Cancer Res. 2000;60:3155-3159.
2. van Schooten FJ, Hirvonen A, Maas LM, De Mol BA, Kleinjans JC, Bell DA and Durrer JD. Putative susceptibility markers of coronary artery disease: association between VDR genotype, smoking, and aromatic DNA adduct levels in human right atrial tissue. FASEB J. 1998;12:1409-1417.
3. Services USDoHaH. The Health Consequences of Smoking—50 Years of Progress: A Report of the Surgeon General. 2014.
4. Zakhari S. Overview: how is alcohol metabolized by the body? Alcohol Res Health. 2006;29:245-254.
5. Mufti SI. Alcohol acts to promote incidence of tumors. Cancer Detect Prev. 1992;16:157-162.
6. Shield KD, Parry C and Rehm J. Chronic diseases and conditions related to alcohol use. Alcohol Res. 2013;35:155-73.
7. Hart CL, Davey Smith G, Gruer L and Watt GC. The combined effect of smoking tobacco and drinking alcohol on cause-specific mortality: a 30 year cohort study. BMC Public Health. 2010;10:789.
8. Klatsky AL, Friedman GD and Siegelaub AB. Alcohol and mortality. A ten-year Kaiser-Permanente experience. Ann Intern Med. 1981;95:139-145.
9. Klatsky AL and Armstrong MA. Alcohol, smoking, coffee, and cirrhosis. Am J Epidemiol. 1992;136:1248-1257.
10. IPCS. Selected non-heterocyclic polycyclic aromatic hydrocarbons. Environmental Health Criteria 202. International Programme on Chemical Safety. World Health Organization Lyon, France; 1998: 883.
11. Gelboin HV. Benzo[alpha]pyrene metabolism, activation and carcinogenesis: role and regulation of mixed-function oxidases and related enzymes. Physiol Rev. 1980;60:1107-1166.
12. Shimada T. Xenobiotic-metabolizing enzymes involved in activation and detoxification of carcinogenic polycyclic aromatic hydrocarbons. Drug Metab Pharmacokinet. 2006;21:257-276.
13. Joseph P and Jaiswal AK. NAD(P)H:quinone oxidoreductase1 (DT diaphorase) specifically prevents the formation of benzo[a]pyrene quinone-DNA adducts generated by cytochrome P4501A1 and P450 reductase. Proc Natl Acad Sci U S A. 1994;91:8413-7.
14. Kohle C and Bock KW. Coordinate regulation of Phase I and II xenobiotic metabolisms by the Ah receptor and Nrf2. Biochem Pharmacol. 2007;73:1853-1862.
15. Miao W, Hu L, Scrivens PJ and Batist G. Transcriptional regulation of NF-E2 p45-related factor (NRF2) expression by the aryl hydrocarbon receptor-xenobiotic response element signaling pathway: direct cross-talk between phase I and II drug-metabolizing enzymes. J Biol Chem. 2005;280:20340-20348.
16. Yeager RL, Reisman SA, Aleksunes LM and Klaassen CD. Introducing the "TCDD-inducible AhR-Nrf2 gene battery". Toxicol Sci. 2009;111:238-246.
17. Jelski W and Szmitkowski M. Alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) in the cancer diseases. Clin Chim Acta. 2008;395:1-5.
18. Nanji AA, Khettry U, Sadrzadeh SM and Yamanaka T. Severity of liver injury in experimental alcoholic liver disease. Correlation with plasma endotoxin, prostaglandin E2, leukotriene B4, and thromboxane B2. Am J Pathol. 1993;142:367-373.
19. Enomoto N, Ikejima K, Yamashina S, Enomoto A, Nishiura T, Nishimura T, Brenner DA, Schemmer P, Bradford BU, Rivera CA, Zhong Z and Thurman RG. Kupffer cell-derived prostaglandin E(2) is involved in alcohol-induced fat accumulation in rat liver. Am J Physiol Gastrointest Liver Physiol. 2000;279:G100-G106.
20. Badawy AA, Doughrty DM, Marsh-Richard DM and Steptoe A. Activation of liver tryptophan pyrrolase mediates the decrease in tryptophan availability to the brain after acute alcohol consumption by normal subjects. Alcohol Alcohol. 2009;44:267-271.
21. Zhang HF, Lin XH, Yang H, Zhou LC, Guo YL, Barnett JV and Guo ZM. Regulation of the Activity and Expression of Aryl Hydrocarbon Receptor by Ethanol in Mouse Hepatic Stellate Cells. Alcohol Clin Exp Res. 2012;36:1873-1881.
22. Dong H, Hao L, Zhang W, Zhong W, Guo W, Yue R, Sun X and Zhou Z. Activation of AhR-NQO1 Signaling Pathway Protects Against Alcohol-Induced Liver Injury by Improving Redox Balance. Cell Mol Gastroenterol Hepatol. 2021;12:793-811.
23. Lin X, Yang H, Zhang H, Zhou L and Guo Z. A novel transcription mechanism activated by ethanol: induction of Slc7a11 gene expression via inhibition of the DNA-binding activity of transcriptional repressor octamer-binding transcription factor 1 (OCT-1). J Biol Chem. 2013;288:14815-14823.
24. Lin X, Yang H, Zhou LC and Guo ZM. Nrf2-Dependent Induction of NQO1 in Mouse Aortic Endothelial Cells Overexpressing Catalase. Free Radic Biol Med. 2011;51:97-106.
25. Zhou LC, Xiang W, Potts J, Floyd M, Sharan K, Yang H, Ross J, Nyanda AM and Guo ZM. Reduction in Extracellular Superoxide Dismutase Activity in African-American Patients with Hypertension. Free Radic Biol Med. 2006;41:1384-1391.
26. Hustad JT and Carey KB. Using calculations to estimate blood alcohol concentrations for naturally occurring drinking episodes: a validity study. J Stud Alcohol. 2005;66:130-138.
27. Lindblad B and Olsson R. Unusually high levels of blood alcohol? JAMA. 1976;236:1600-1602.
28. O'Neill S, Tipton KF, Prichard JS and Quinlan A. Survival after high blood alcohol levels. Association with first-order elimination kinetics. Arch Intern Med. 1984;144:641-642.
29. Roberts LJ and Morrow JD. Isoprostanes. Novel markers of endogenous lipid peroxidation and potential mediators of oxidant injury. Ann N Y Acad Sci. 1994;744:237-242.
30. Baird L and Yamamoto M. The Molecular Mechanisms Regulating the KEAP1-NRF2 Pathway. Mol Cell Biol. 2020;40.
31. Lu Y, Zhang XH and Cederbaum AI. Ethanol induction of CYP2A5: role of CYP2E1-ROS-Nrf2 pathway. Toxicol Sci. 2012;128:427-38.
32. He F, Ru X and Wen T. NRF2, a Transcription Factor for Stress Response and Beyond. Int J Mol Sci. 2020;21.
33. Hankinson O. The aryl hydrocarbon receptor complex. Annu Rev Pharmacol Toxicol. 1995;35:307-340.
34. Nebert DW and Karp CL. Endogenous functions of the aryl hydrocarbon receptor (AHR): intersection of cytochrome P450 1 (CYP1)-metabolized eicosanoids and AHR biology. J Biol Chem. 2008;283:36061-36065.
35. Abbott BD, Perdew GH and Birnbaum LS. Ah receptor in embryonic mouse palate and effects of TCDD on receptor expression. Toxicol Appl Pharmacol. 1994;126:16-25.
36. Wang Z, Yang H, Ramesh A, Roberts LJ, Zhou L, Lin X, Zhao Y and Guo Z. Overexpression of Cu/Zn-superoxide dismutase and/or catalase accelerates benzo(a)pyrene detoxification by upregulation of the aryl hydrocarbon receptor in mouse endothelial cells. Free Radic Biol Med. 2009;47:1221-1229.
37. Ross D and Siegel D. The diverse functionality of NQO1 and its roles in redox control. Redox Biol. 2021;41:101950.
38. Barnes SL, Singletary KW and Frey R. Ethanol and acetaldehyde enhance benzo[a]pyrene-DNA adduct formation in human mammary epithelial cells. Carcinogenesis. 2000;21:2123-2128.
39. Ahrendt SA, Chow JT, Yang SC, Wu L, Zhang MJ, Jen J and Sidransky D. Alcohol consumption and cigarette smoking increase the frequency of p53 mutations in non-small cell lung cancer. Cancer Res. 2000;60:3155-3159.