NF-κB-mediated regulation of rat CYP2E1 by two independent signaling pathways


Autoři: Qin Lin aff001;  Xiaolin Kang aff001;  Xuefeng Li aff001;  Tao Wang aff001;  Fengting Liu aff001;  Jinxue Jia aff001;  Ziqi Jin aff001;  Yongzhi Xue aff001
Působiště autorů: Institute of Pharmacokinetics and Liver Molecular Pharmacology, Department of Pharmacology, Baotou Medical College, Baotou, Inner Mongolia, China aff001
Vyšlo v časopise: PLoS ONE 14(12)
Kategorie: Research Article
doi: 10.1371/journal.pone.0225531

Souhrn

Cytochrome P450 2E1 (CYP2E1) plays an important role in both alcohol-induced and immune-mediated liver injury. However, the mechanism underlying CYP2E1 transcriptional regulation has not been clarified. This study focused on the NF-κB-mediated transcriptional regulation of rat CYP2E1 by two independent signaling pathways in alcohol-induced and immune-mediated liver injury rat models. Male Sprague-Dawley rats were used in pharmacokinetic, molecular pharmacology, and morphology experiments. A rat model of alcohol-induced liver injury (AL) was established by feeding an ethanol-containing diet (42 g/kg/day) for 5 weeks as indicated. A rat immune-mediated liver injury (IM) model was established by the sequential injection of bacillus Calmette-Guérin (BCG, 125 mg/kg, once) via the tail vein after test day 21 and 10 μg/kg LPS 13 days later. HPLC, real-time PCR, western blot and ELISA analyses were performed. CYP2E1 expression was enhanced during the process of alcohol-induced liver injury (increased by 56%, P < 0.05) and significantly reduced during that of immune-mediated liver injury (reducedby52%, P < 0.05). NF-κB was activated in both the AL and IM groups (increased by 56% and76%, respectively, P < 0.05). Compared to those in the livers of AL model rats, the interleukin (IL)-1β, tumor necrosis factor (TNF)-α, and iNOS levels in IM model rat livers were increased (increased by 26%, 21% and 101%, respectively, P < 0.05). The differential changes in CYP2E1 in the processes of alcohol-induced and immune-mediated liver injury may result from the differential expression of inflammatory cytokines and iNOS after NF-κB activation, leading to the NF-κB-mediated transcriptional regulation of rat CYP2E1 by two independent signaling pathways.

Klíčová slova:

Analysis of variance – Blood plasma – Cytokines – Drug metabolism – Enzyme-linked immunoassays – Fatty liver – Inflammation – Transcriptional control


Zdroje

1. Morgan ET. Impact of infectious and inflammatory disease on cytochrome P450-mediated drug metabolism and pharmacokinetics. Clinical pharmacology and therapeutics. 2009;85(4):434–8. Epub 2009/02/13. doi: 10.1038/clpt.2008.302 19212314

2. Seitz HK, Mueller S. [The role of Cytochrom P4502E1 in Alcoholic Liver Disease and alcohol mediated carcinogenesis]. Zeitschrift fur Gastroenterologie. 2019;57(1):37–45. Epub 2019/01/15. doi: 10.1055/a-0784-8815 30641601.

3. Mimche SM, Nyagode BA, Merrell MD, Lee CM, Prasanphanich NS, Cummings RD, et al. Hepatic cytochrome P450s, phase II enzymes and nuclear receptors are downregulated in a Th2 environment during Schistosoma mansoni infection. Drug metabolism and disposition: the biological fate of chemicals. 2014;42(1):134–40. Epub 2013/10/29. doi: 10.1124/dmd.113.054957 24163175

4. Kinloch RD, Lee CM, van Rooijen N, Morgan ET. Selective role for tumor necrosis factor-alpha, but not interleukin-1 or Kupffer cells, in down-regulation of CYP3A11 and CYP3A25 in livers of mice infected with a noninvasive intestinal pathogen. Biochemical pharmacology. 2011;82(3):312–21. Epub 2011/05/17. doi: 10.1016/j.bcp.2011.04.016 21570957

5. Dou X, Li S, Wang Z, Gu D, Shen C, Yao T, et al. Inhibition of NF-kappaB activation by 4-hydroxynonenal contributes to liver injury in a mouse model of alcoholic liver disease. The American journal of pathology. 2012;181(5):1702–10. Epub 2012/09/18. doi: 10.1016/j.ajpath.2012.08.004 22982442

6. Cederbaum AI, Lu Y, Wang X, Wu D. Synergistic toxic interactions between CYP2E1, LPS/TNFalpha, and JNK/p38 MAP kinase and their implications in alcohol-induced liver injury. Advances in experimental medicine and biology. 2015;815:145–72. Epub 2014/11/28. doi: 10.1007/978-3-319-09614-8_9 25427906.

7. Qin JD, Cao ZH, Li XF, Kang XL, Xue Y, Li YL, et al. Effect of ammonium pyrrolidine dithiocarbamate (PDTC) on NF-kappaB activation and CYP2E1 content of rats with immunological liver injury. Pharmaceutical biology. 2014;52(11):1460–6. Epub 2014/06/26. doi: 10.3109/13880209.2014.898075 24963944.

8. Correa M, Viaggi C, Escrig MA, Pascual M, Guerri C, Vaglini F, et al. Ethanol intake and ethanol-induced locomotion and locomotor sensitization in Cyp2e1 knockout mice. Pharmacogenetics and genomics. 2009;19(3):217–25. Epub 2009/01/30. doi: 10.1097/FPC.0b013e328324e726 19177030.

9. Butura A, Nilsson K, Morgan K, Morgan TR, French SW, Johansson I, et al. The impact of CYP2E1 on the development of alcoholic liver disease as studied in a transgenic mouse model. Journal of hepatology. 2009;50(3):572–83. Epub 2009/01/23. doi: 10.1016/j.jhep.2008.10.020 19157621.

10. McClain CJ, Song Z, Barve SS, Hill DB, Deaciuc I. Recent advances in alcoholic liver disease. IV. Dysregulated cytokine metabolism in alcoholic liver disease. American journal of physiology Gastrointestinal and liver physiology. 2004;287(3):G497–502. Epub 2004/08/28. doi: 10.1152/ajpgi.00171.2004 15331349.

11. Morgan ET, Dempsey JL, Mimche SM, Lamb TJ, Kulkarni S, Cui JY, et al. Physiological Regulation of Drug Metabolism and Transport: Pregnancy, Microbiome, Inflammation, Infection, and Fasting. Drug metabolism and disposition: the biological fate of chemicals. 2018;46(5):503–13. Epub 2018/03/09. doi: 10.1124/dmd.117.079905 29514828

12. Wang F, Liu JC, Zhou RJ, Zhao X, Liu M, Ye H, et al. Apigenin protects against alcohol-induced liver injury in mice by regulating hepatic CYP2E1-mediated oxidative stress and PPARalpha-mediated lipogenic gene expression. Chemico-biological interactions. 2017;275:171–7. Epub 2017/08/15. doi: 10.1016/j.cbi.2017.08.006 28803762.

13. Rasineni K, Penrice DD, Natarajan SK, McNiven MA, McVicker BL, Kharbanda KK, et al. Alcoholic vs non-alcoholic fatty liver in rats: distinct differences in endocytosis and vesicle trafficking despite similar pathology. BMC gastroenterology. 2016;16:27. Epub 2016/03/01. doi: 10.1186/s12876-016-0433-4 26924554

14. Rahmani AH, Almatroudi A, Babiker AY, Khan AA, Alsahli MA. Thymoquinone, an Active Constituent of Black Seed Attenuates CCl4 Induced Liver Injury in Mice via Modulation of Antioxidant Enzymes, PTEN, P53 and VEGF Protein. Open access Macedonian journal of medical sciences. 2019;7(3):311–7. Epub 2019/03/06. doi: 10.3889/oamjms.2019.050 30833993

15. Bedada SK, Neerati P. Resveratrol Pretreatment Affects CYP2E1 Activity of Chlorzoxazone in Healthy Human Volunteers. Phytotherapy research: PTR. 2016;30(3):463–8. Epub 2015/12/19. doi: 10.1002/ptr.5549 26680654.

16. Wang F, Xue Y, Yang J, Lin F, Sun Y, Li T, et al. Hepatoprotective effect of apple polyphenols against concanavalin A-induced immunological liver injury in mice. Chemico-biological interactions. 2016;258:159–65. Epub 2016/08/29. doi: 10.1016/j.cbi.2016.08.018 27567545.

17. Zhai JX, Zhang ZX, Feng YJ, Ding SS, Wang XH, Zou LW, et al. PDTC attenuate LPS-induced kidney injury in systemic lupus erythematosus-prone MRL/lpr mice. Molecular biology reports. 2012;39(6):6763–71. Epub 2012/02/10. doi: 10.1007/s11033-012-1501-7 22318546.

18. Jiang J, Mathijs K, Timmermans L, Claessen SM, Hecka A, Weusten J, et al. Omics-based identification of the combined effects of idiosyncratic drugs and inflammatory cytokines on the development of drug-induced liver injury. Toxicology and applied pharmacology. 2017;332:100–8. Epub 2017/07/25. doi: 10.1016/j.taap.2017.07.014 28733206.

19. Ko JW, Shin JY, Kim JW, Park SH, Shin NR, Lee IC, et al. Protective effects of diallyl disulfide against acetaminophen-induced nephrotoxicity: A possible role of CYP2E1 and NF-kappaB. Food and chemical toxicology: an international journal published for the British Industrial Biological Research Association. 2017;102:156–65. Epub 2017/02/22. doi: 10.1016/j.fct.2017.02.021 28219698.

20. Park JW, Lee CM, Cheng JS, Morgan ET. Posttranslational regulation of CYP2J2 by nitric oxide. Free radical biology & medicine. 2018;121:149–56. Epub 2018/05/02. doi: 10.1016/j.freeradbiomed.2018.04.576 29715548

21. Bai F, Huang Q, Wei J, Lv S, Chen Y, Liang C, et al. Gypsophila elegans isoorientin-2''-O-alpha-l-arabinopyranosyl ameliorates porcine serum-induced immune liver fibrosis by inhibiting NF-kappaB signaling pathway and suppressing HSC activation. International immunopharmacology. 2018;54:60–7. Epub 2017/11/07. doi: 10.1016/j.intimp.2017.10.028 29107862.

22. Li L, Wu Y, Yin F, Feng Q, Dong X, Zhang R, et al. Fructose 1, 6-diphosphate prevents alcohol-induced liver injury through inhibiting oxidative stress and promoting alcohol metabolism in mice. European journal of pharmacology. 2017;815:274–81. Epub 2017/09/26. doi: 10.1016/j.ejphar.2017.09.034 28943104.

23. Choi EK, Baek J, Park S, Baek SH, Choi JH, Lee CH, et al. Preischemic transfusion of old packed RBCs exacerbates early-phase warm hepatic ischemia reperfusion injury in rats. The Journal of surgical research. 2018;222:26–33. Epub 2017/12/24. doi: 10.1016/j.jss.2017.09.017 29273372.

24. Lee CM, Lee BS, Arnold SL, Isoherranen N, Morgan ET. Nitric oxide and interleukin-1beta stimulate the proteasome-independent degradation of the retinoic acid hydroxylase CYP2C22 in primary rat hepatocytes. The Journal of pharmacology and experimental therapeutics. 2014;348(1):141–52. Epub 2013/10/23. doi: 10.1124/jpet.113.209841 24144795

25. Sun H, Lee CM, Tripathi S, Kim KB, Morgan ET. Nitric oxide-dependent CYP2B degradation is potentiated by a cytokine-regulated pathway and utilizes the immunoproteasome subunit LMP2. The Biochemical journal. 2012;445(3):377–82. Epub 2012/05/23. doi: 10.1042/BJ20120820 22612225

26. Wang D, Gao Q, Wang T, Zhao G, Qian F, Huang J, et al. Green tea infusion protects against alcoholic liver injury by attenuating inflammation and regulating the PI3K/Akt/eNOS pathway in C57BL/6 mice. Food & function. 2017;8(9):3165–77. Epub 2017/08/08. doi: 10.1039/c7fo00791d 28782772.

27. Jung YS, Kim SJ, Kwon DY, Ahn CW, Kim YS, Choi DW, et al. Alleviation of alcoholic liver injury by betaine involves an enhancement of antioxidant defense via regulation of sulfur amino acid metabolism. Food and chemical toxicology: an international journal published for the British Industrial Biological Research Association. 2013;62:292–8. Epub 2013/09/03. doi: 10.1016/j.fct.2013.08.049 23994088.

28. Tindberg N, Bengtsson I, Hu Y. A novel lipopolysaccharide-modulated Jun binding repressor in intron 2 of CYP2E1. Journal of neurochemistry. 2004;89(6):1336–46. Epub 2004/06/11. doi: 10.1111/j.1471-4159.2004.02449.x 15189336.

29. Markovic J, Stosic M, Kojic D, Matavulj M. Effects of acrylamide on oxidant/antioxidant parameters and CYP2E1 expression in rat pancreatic endocrine cells. Acta histochemica. 2018;120(2):73–83. Epub 2017/12/12. doi: 10.1016/j.acthis.2017.12.001 29224921.

30. Moncion A, Truong NT, Garrone A, Beaune P, Barouki R, De Waziers I. Identification of a 16-nucleotide sequence that mediates post-transcriptional regulation of rat CYP2E1 by insulin. The Journal of biological chemistry. 2002;277(48):45904–10. Epub 2002/09/25. doi: 10.1074/jbc.M207841200 12270935.

31. Rasineni K, Thomes PG, Kubik JL, Harris EN, Kharbanda KK, Casey CA. Chronic alcohol exposure alters circulating insulin and ghrelin levels: role of ghrelin in hepatic steatosis. American journal of physiology Gastrointestinal and liver physiology. 2019;316(4):G453–g61. Epub 2019/02/01. doi: 10.1152/ajpgi.00334.2018 30702902

32. Nelson NG, Suhaidi FA, Law WX, Liang NC. Chronic moderate alcohol drinking alters insulin release without affecting cognitive and emotion-like behaviors in rats. Alcohol (Fayetteville, NY). 2018;70:11–22. Epub 2018/05/02. doi: 10.1016/j.alcohol.2017.12.001 29709884.

33. Jin M, Ande A, Kumar A, Kumar S. Regulation of cytochrome P450 2e1 expression by ethanol: role of oxidative stress-mediated pkc/jnk/sp1 pathway. Cell death & disease. 2013;4:e554. Epub 2013/03/23. doi: 10.1038/cddis.2013.78 23519123


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2019 Číslo 12