Glucocorticoid receptor contributes to the altered expression of hepatic cytochrome P450 upon cigarette smoking

Li,Xue; Yan,Zhongfang; Wu,Qi; Sun,Xin; Li,Fan; Zhang,Subei; Li,Kuan; Li,Li; Wu,Junping; Xu,Long; Feng,Jing; Ning,Wen; Liu,Zhixue; Chen,Huaiyong

doi:10.3892/mmr.2016.5898

Glucocorticoid receptor contributes to the altered expression of hepatic cytochrome P450 upon cigarette smoking

Authors:
- Xue Li
- Zhongfang Yan
- Qi Wu
- Xin Sun
- Fan Li
- Subei Zhang
- Kuan Li
- Li Li
- Junping Wu
- Long Xu
- Jing Feng
- Wen Ning
- Zhixue Liu
- Huaiyong Chen
View Affiliations

Affiliations: Department of Basic Medicine Laboratory, Tianjin Institute of Respiratory Diseases, Tianjin Haihe Hospital, Tianjin 300350, P.R. China, Department of Respiratory, Tianjin Haihe Hospital, Tianjin 300350, P.R. China, Department of Respiratory, Tianjin Medical University General Hospital, Tianjin 30005, P.R. China, State Key Laboratory of Medicinal Chemical Biology, College of Life Sciences, Nankai University, Tianjin 300071, P.R. China, Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Graduate School of The Chinese Academy of Sciences, Shanghai 200031, P.R. China
Published online on: October 27, 2016 https://doi.org/10.3892/mmr.2016.5898
Pages: 5271-5280

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Cigarette smoking has been shown to cause pathological alterations in the liver. However, how hepatic metabolism is altered during cigarette smoking‑induced inflammation remains to be fully elucidated. In the present study, a rat model of smoking was established to examine the effects of cigarette smoking on inflammation, autophagy activity, and the expression of nuclear receptor and CYP in the liver. Elevated expression of interleukin 1β and activation of autophagy in the liver were observed upon smoking exposure in rats. Cigarette smoking induced a significant reduction in the mRNA expression levels of cytochromes, including cytochrome P450 (Cyp)1A2, Cyp2D4 and Cyp3A2. Accordingly, a decrease was also observed in glucocorticoid receptor (GR), a regulator of the expression of Cyp. Activation of the GR signal in human hepatic LO2 cells did not affect autophagic genes, however, it led to the upregulation of hCYP1A2, hCYP2C19 and hCYP3A4, and the downregulation of hCYP2C9. The GR antagonist, RU486, eliminated this effect, suggesting the importance of GR in liver metabolism upon cigarette smoking.

View Figures

View References

1	Kleinstreuer C and Feng Y: Lung deposition analyses of inhaled toxic aerosols in conventional and less harmful cigarette smoke: a review. International journal of environmental research and public health. 10:4454–4485. 2013. View Article : Google Scholar : PubMed/NCBI
2	Altamirano J and Bataller R: Cigarette smoking and chronic liver diseases. Gut. 59:1159–1162. 2010. View Article : Google Scholar : PubMed/NCBI
3	Bataller R: Time to ban smoking in patients with chronic liver diseases. Hepatology. 44:1394–1396. 2006. View Article : Google Scholar : PubMed/NCBI
4	Alebiosu CO: An update on ‘progression promoters’ in renal diseases. J Natl Med Assoc. 95:30–42. 2003.PubMed/NCBI
5	Malfertheiner P and Schütte K: Smoking-a trigger for chronic inflammation and cancer development in the pancreas. Am J Gastroenterol. 101:160–162. 2006. View Article : Google Scholar : PubMed/NCBI
6	Gershwin ME, Selmi C, Worman HJ, Gold EB, Watnik M, Utts J, Lindor KD, Kaplan MM and Vierling JM: USA PBC Epidemiology Group: Risk factors and comorbidities in primary biliary cirrhosis: A controlled interview-based study of 1032 patients. Hepatology. 42:1194–1202. 2005. View Article : Google Scholar : PubMed/NCBI
7	Mallat A, Hezode C and Lotersztajn S: Environmental factors as disease accelerators during chronic hepatitis C. J Hepatol. 48:657–665. 2008. View Article : Google Scholar : PubMed/NCBI
8	Azzalini L, Ferrer E, Ramalho LN, Moreno M, Domínguez M, Colmenero J, Peinado VI, Barberà JA, Arroyo V, Ginès P, et al: Cigarette smoking exacerbates nonalcoholic fatty liver disease in obese rats. Hepatology. 51:1567–1576. 2010. View Article : Google Scholar : PubMed/NCBI
9	Koh WP, Robien K, Wang R, Govindarajan S, Yuan JM and Yu MC: Smoking as an independent risk factor for hepatocellular carcinoma: The Singapore Chinese health study. Br J Cancer. 105:1430–1435. 2011. View Article : Google Scholar : PubMed/NCBI
10	Zordoky BN, Aboutabl ME and El-Kadi AO: Modulation of cytochrome P450 gene expression and arachidonic acid metabolism during isoproterenol-induced cardiac hypertrophy in rats. Drug Metab Dispos. 36:2277–2286. 2008. View Article : Google Scholar : PubMed/NCBI
11	Danielson PB: The cytochrome P450 superfamily: Biochemistry, evolution and drug metabolism in humans. Curr Drug Metab. 3:561–597. 2002. View Article : Google Scholar : PubMed/NCBI
12	Guengerich FP: Cytochrome P450s and other enzymes in drug metabolism and toxicity. AAPS J. 8:E101–E111. 2006. View Article : Google Scholar : PubMed/NCBI
13	Martínez-Jimúnez CP, Jover R, Donato MT, Castell JV and Gómez-Lechón MJ: Transcriptional regulation and expression of CYP3A4 in hepatocytes. Curr Drug Metab. 8:185–194. 2007. View Article : Google Scholar : PubMed/NCBI
14	Bell JC and Strobel HW: Regulation of cytochrome P450 4F11 by nuclear transcription factor-kappaB. Drug metabolism and disposition: the biological fate of chemicals. 40:205–211. 2012. View Article : Google Scholar : PubMed/NCBI
15	Nannelli A, Chirulli V, Longo V and Gervasi PG: Expression and induction by rifampicin of CAR- and PXR-regulated CYP2B and CYP3A in liver, kidney and airways of pig. Toxicology. 252:105–112. 2008. View Article : Google Scholar : PubMed/NCBI
16	Goodwin B, Hodgson E, D'Costa DJ, Robertson GR and Liddle C: Transcriptional regulation of the human CYP3A4 gene by the constitutive androstane receptor. Mol Pharmacol. 62:359–365. 2002. View Article : Google Scholar : PubMed/NCBI
17	Pascussi JM, Gerbal-Chaloin S, Drocourt L, Maurel P and Vilarem MJ: The expression of CYP2B6, CYP2C9 and CYP3A4 genes: A tangle of networks of nuclear and steroid receptors. Biochim Biophys Acta. 1619:243–253. 2003. View Article : Google Scholar : PubMed/NCBI
18	Gerbal-Chaloin S, Daujat M, Pascussi JM, Pichard-Garcia L, Vilarem MJ and Maurel P: Transcriptional regulation of CYP2C9 gene. Role of glucocorticoid receptor and constitutive androstane receptor. J Biol Chem. 277:209–217. 2002. View Article : Google Scholar : PubMed/NCBI
19	Cooper BW, Cho TM, Thompson PM and Wallace AD: Phthalate induction of CYP3A4 is dependent on glucocorticoid regulation of PXR expression. Toxicol Sci. 103:268–277. 2008. View Article : Google Scholar : PubMed/NCBI
20	Moszczyński P, Zabiński Z, Moszczyński P Jr, Rutowski J, Słowinski S and Tabarowski Z: Immunological findings in cigarette smokers. Toxicol Lett. 118:121–127. 2001. View Article : Google Scholar : PubMed/NCBI
21	Ryter SW and Choi AM: Autophagy in the lung. Proc Am Thorac Soc. 7:13–21. 2010. View Article : Google Scholar : PubMed/NCBI
22	Czaja MJ, Ding WX, Donohue TM Jr, Friedman SL, Kim JS, Komatsu M, Lemasters JJ, Lemoine A, Lin JD, Ou JH, et al: Functions of autophagy in normal and diseased liver. Autophagy. 9:1131–1158. 2013. View Article : Google Scholar : PubMed/NCBI
23	Guo R, Xu X, Babcock SA, Zhang Y and Ren J: Aldehyde dedydrogenase-2 plays a beneficial role in ameliorating chronic alcohol-induced hepatic steatosis and inflammation through regulation of autophagy. J Hepatol. 62:647–656. 2015. View Article : Google Scholar : PubMed/NCBI
24	Li H, Wu Q, Xu L, Li X, Duan J, Zhan J, Feng J, Sun X and Chen H: Increased oxidative stress and disrupted small intestinal tight junctions in cigarette smoke-exposed rats. Mol Med Rep. 11:4639–4644. 2015.PubMed/NCBI
25	Corpechot C, Gaouar F, Chrétien Y, Johanet C, Chazouillères O and Poupon R: Smoking as an independent risk factor of liver fibrosis in primary biliary cirrhosis. J Hepatol. 56:218–224. 2012. View Article : Google Scholar : PubMed/NCBI
26	Slaviero KA, Clarke SJ and Rivory LP: Inflammatory response: An unrecognised source of variability in the pharmacokinetics and pharmacodynamics of cancer chemotherapy. Lancet Oncol. 4:224–232. 2003. View Article : Google Scholar : PubMed/NCBI
27	Aitken AE, Richardson TA and Morgan ET: Regulation of drug-metabolizing enzymes and transporters in inflammation. Annu Rev Pharmacol Toxicol. 46:123–149. 2006. View Article : Google Scholar : PubMed/NCBI
28	Pondugula SR, Dong H and Chen T: Phosphorylation and protein-protein interactions in PXR-mediated CYP3A repression. Expert Opin Drug Metab Toxicol. 5:861–873. 2009. View Article : Google Scholar : PubMed/NCBI
29	Chai XJ, Zeng S and Xie W: Nuclear receptors PXR and CAR: Implications for drug metabolism regulation, pharmacogenomics and beyond. Expert Opin Drug Metab Toxicol. 9:253–266. 2013. View Article : Google Scholar : PubMed/NCBI
30	Shah P, Guo T, Moore DD and Ghose R: Role of constitutive androstane receptor in Toll-like receptor-mediated regulation of gene expression of hepatic drug-metabolizing enzymes and transporters. Drug Metab Dispos. 42:172–181. 2014. View Article : Google Scholar : PubMed/NCBI
31	Samer CF, Lorenzini KI, Rollason V, Daali Y and Desmeules JA: Applications of CYP450 testing in the clinical setting. Mol Diagn Ther. 17:165–184. 2013. View Article : Google Scholar : PubMed/NCBI
32	Zanger UM and Schwab M: Cytochrome P450 enzymes in drug metabolism: Regulation of gene expression, enzyme activities, and impact of genetic variation. Pharmacol Ther. 138:103–141. 2013. View Article : Google Scholar : PubMed/NCBI
33	Kelly SL and Kelly DE: Microbial cytochromes P450: Biodiversity and biotechnology. Where do cytochromes P450 come from, what do they do and what can they do for us? Philos Trans R Soc Lond B Biol Sci. 368:201204762013.
34	Washko GR, Hunninghake GM, Fernandez IE, Nishino M, Okajima Y, Yamashiro T, Ross JC, Estépar RS, Lynch DA, Brehm JM, et al: Lung volumes and emphysema in smokers with interstitial lung abnormalities. N Engl J Med. 364:897–906. 2011. View Article : Google Scholar : PubMed/NCBI
35	Hussain T, Al-Attas OS, Al-Daghri NM, Mohammed AA, De Rosas E, Ibrahim S, Vinodson B, Ansari MG and El-Din KI: Induction of CYP1A1, CYP1A2, CYP1B1, increased oxidative stress and inflammation in the lung and liver tissues of rats exposed to incense smoke. Mol Cell Biochem. 391:127–136. 2014. View Article : Google Scholar : PubMed/NCBI
36	Minakata Y, Ueda H, Akamatsu K, Kanda M, Yanagisawa S, Ichikawa T, Koarai A, Hirano T, Sugiura H, Matsunaga K and Ichinose M: High COPD prevalence in patients with liver disease. Intern Med. 49:2687–2691. 2010. View Article : Google Scholar : PubMed/NCBI
37	Ivanenkov YA, Balakin KV and Lavrovsky Y: Small molecule inhibitors of NF-kB and JAK/STAT signal transduction pathways as promising anti-inflammatory therapeutics. Mini Rev Med Chem. 11:55–78. 2011. View Article : Google Scholar : PubMed/NCBI
38	Assenat E, Gerbal-Chaloin S, Larrey D, Saric J, Fabre JM, Maurel P, Vilarem MJ and Pascussi JM: Interleukin 1beta inhibits CAR-induced expression of hepatic genes involved in drug and bilirubin clearance. Hepatology. 40:951–960. 2004. View Article : Google Scholar : PubMed/NCBI
39	Widen C, Gustafsson JA and Wikström AC: Cytosolic glucocorticoid receptor interaction with nuclear factor-kappa B proteins in rat liver cells. Biochem J. 373:211–220. 2003. View Article : Google Scholar : PubMed/NCBI
40	Beigneux AP, Moser AH, Shigenaga JK, Grunfeld C and Feingold KR: Reduction in cytochrome P-450 enzyme expression is associated with repression of CAR (constitutive androstane receptor) and PXR (pregnane X receptor) in mouse liver during the acute phase response. Biochem Biophys Res Commun. 293:145–149. 2002. View Article : Google Scholar : PubMed/NCBI
41	Gu X, Ke S, Liu D, Sheng T, Thomas PE, Rabson AB, Gallo MA, Xie W and Tian Y: Role of NF-kappaB in regulation of PXR-mediated gene expression: A mechanism for the suppression of cytochrome P-450 3A4 by proinflammatory agents. J Biol Chem. 281:17882–17889. 2006. View Article : Google Scholar : PubMed/NCBI
42	Wang YM, Ong SS, Chai SC and Chen T: Role of CAR and PXR in xenobiotic sensing and metabolism. Expert Opin Drug Metab Toxicol. 8:803–817. 2012. View Article : Google Scholar : PubMed/NCBI
43	Vrzal R, Stejskalova L, Monostory K, Maurel P, Bachleda P, Pavek P and Dvorak Z: Dexamethasone controls aryl hydrocarbon receptor (AhR)-mediated CYP1A1 and CYP1A2 expression and activity in primary cultures of human hepatocytes. Chem Biol Interact. 179:288–296. 2009. View Article : Google Scholar : PubMed/NCBI
44	Schneider JL and Cuervo AM: Liver autophagy: Much more than just taking out the trash. Nat Rev Gastroenterol Hepatol. 11:187–200. 2014. View Article : Google Scholar : PubMed/NCBI
45	Marino G, Niso-Santano M, Baehrecke EH and Kroemer G: Self-consumption: The interplay of autophagy and apoptosis. Nat Rev Mol Cell Biol. 15:81–94. 2014. View Article : Google Scholar : PubMed/NCBI