Advances in Clinical and Experimental Medicine

Title abbreviation: Adv Clin Exp Med
JCR Impact Factor (IF) – 1.736
5-Year Impact Factor – 2.135
Index Copernicus  – 168.52
MEiN – 70 pts

ISSN 1899–5276 (print)
ISSN 2451-2680 (online)
Periodicity – monthly

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Advances in Clinical and Experimental Medicine

2019, vol. 28, nr 9, September, p. 1237–1241

doi: 10.17219/acem/105852

Publication type: original article

Language: English

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NFE2L2 is associated with NQO1 expression and low stage of hepatic fibrosis in patients with chronic hepatitis C

Kamila Małgorzata Wójcik1,A,B,C,D,E,F, Anna Piekarska1,E,F, Bożena Szymańska2,C, Elżbieta Jabłonowska2,A,B,C,D,E,F

1 Department of Infectious Diseases and Hepatology, Medical University of Lodz, Poland

2 Central Laboratory, Medical University of Lodz, Poland

Abstract

Background. Oxidative stress is extremely important in the pathogenesis of chronic hepatitis C virus (HCV). In response to oxidative stress, adaptive antioxidant defenses are upregulated in the liver. The balance between antioxidant response and oxidative stress plays a key role in hepatic injury in HCV infection.
Objectives. The objective of this study was to assess the hepatic expression of the antioxidant genes GFER (growth factor erv1-like) and NQO1 (NAD(P)H:quinone oxidoreductase-1) and the regulatory gene NFE2L2 (nuclear factor erythroid 2-related factor-2) in liver biopsy specimens obtained from chronic HCV patients with regard to selected clinical parameters and histology, and to determine whether GFER and NQO1 expression is dependent on NFE2L2.
Material and Methods. The study group consisted of 42 patients with chronic HCV. Reverse transcription polymerase chain reaction (RT-PCR) was used to analyze the expression of antioxidant and regulatory genes in liver biopsy samples.
Results. Positive correlation was observed between the hepatic expression of NFE2L2 and NQO1 in the chronic HCV patients (p < 0.0001). The hepatic expression of NFE2L2 was significantly lower in patients with advanced liver fibrosis (p = 0.05). However, there was no significant difference in the hepatic expression of GFER and NQO1 in relation to the progression of liver steatosis, inflammation and fibrosis.
Conclusion. The hepatic expression of NFE2L2 is associated with NQO1 and low stage of hepatic fibrosis in patients infected with HCV.

Key words

hepatitis C, liver fibrosis, antioxidant genes, regulatory gene

References (26)

  1. Chen SL, Morgan TR. The natural history of hepatitis C virus (HCV) infection. Int J Med Sci. 2006;3(2):47–52.
  2. Lauer GM, Walker BD. Hepatitis C virus infection. N Engl J Med. 2001;345(1):41–52.
  3. Tanikawa K, Torimura T. Studies on oxidative stress in liver diseases: Important future trends in liver research. Med Mol Morphol. 2006;39(1):22–27.
  4. Clement S, Pascarella S, Negro F. Hepatitis C virus infection: Molecular pathways to steatosis, insulin resistance and oxidative stress. Viruses. 2009;1(2):126–143.
  5. Okuda M, Li K, Beard MR, et al. Mitochondrial injury, oxidative stress, and antioxidant gene expression are induced by hepatitis C virus core protein. Gastroenterology. 2002;122(2):366–375.
  6. Zhu H, Li Y. NAD(P)H: Quinone oxidoreductase 1 and its potential protective role in cardiovascular diseases and related conditions. Cardiovasc Toxicol. 2012;12(1):39–45.
  7. Francavilla A, Hagiya M, Porter KA, Polimeno L, Ihara I, Starzl TE. Augmenter of liver regeneration: Its place in the universe of hepatic growth factors. Hepatology. 1994;20(3):747–757.
  8. Mitochondrially associated hepatitis B virus X protein constitutively activates transcription factors STAT-3 and NF-kappa B via oxidative stress. Mol Cell Biol. 2001;21(22):7721–7730.
  9. Masalova OV, Kochetkov SN, Isaguliants MG. Hepatitis C virus proteins activate NRF2/ARE pathway by distinct ROS-dependent and independent mechanisms in HUH7 cells. PLoS One. 2011;6(9):249–257.
  10. Farinati F, Cardin R, De Maria N, et al. Iron storage, lipid peroxidation and glutathione turnover in chronic anti-HCV positive hepatitis. J Hepatol. 1995;22(4):449–456.
  11. Qadri I, Iwahashi M, Capasso JM, et al. Induced oxidative stress and activated expression of manganese superoxide dismutase during hepatitis C virus replication: Role of JNK, p38 MAPK and AP-1. Biochem J. 2004;15(3):919–928.
  12. Wen F, Brown KE, Britigan BE, Schmidt WN. Hepatitis C core protein inhibits induction of heme oxygenase-1 and sensitizes hepatocytes to cytotoxicity. Cell Biol Toxicol. 2008;24(2):175–188.
  13. Carvajal-Yepes M, Himmelsbach K, Schaedler S, et al. Hepatitis C virus impairs the induction of cytoprotective Nrf2 target genes by delocalization of small Maf proteins. J Biol Chem. 2011;18(286):8941–8951.
  14. Swietek K, Juszczyk J. Reduced glutathione concentration in erythrocytes of patients with acute and chronic viral hepatitis. J Viral Hepat. 1997;4(2):139–141.
  15. Venturini D, Simao AN, Barbosa DS, et al. Increased oxidative stress, decreased total antioxidant capacity, and iron overload in untreated patients with chronic hepatitis C. Dig Dis Sci. 2010;55(4):1120–1127.
  16. Zhu Z, Wilson AT, Mathahs MM, et al. Heme oxygenase-1 suppresses hepatitis C virus replication and increases resistance of hepatocytes to oxidant injury. Hepatology. 2008;48(5):1430–1439.
  17. Ghaziani T, Shan Y, Lambrecht RW, et al. HCV proteins increase expression of heme oxygenase-1 (HO-1) and decrease expression of Bach1 in human hepatoma cells. J Hepatol. 2006;45(1):5–12.
  18. Sass G, Soares MC, Yamashita K, et al. Heme oxygenase-1 and its reaction product, carbon monoxide, prevent inflammation-related apoptotic liver damage in mice. Hepatology. 2003;38(4):909–918.
  19. Kumar S, Wang J, Rani R, Gandhi CR. Hepatic deficiency of augmenter of liver regeneration exacerbates alcohol-induced liver injury and promotes fibrosis in mice. PLoS One. 2016;25(1):e0147864.
  20. Cheng ML, Lu YF, Chen H, Shen ZY, Liu J. Liver expression of Nrf2-related genes in different liver diseases. Hepatobiliary Pancreat Dis Int. 2015;14(5):485–491.
  21. Choi HK, Pokharel YR, Lim SC, et al. Inhibition of liver fibrosis by solubilized coenzyme Q10: Role of Nrf2 activation in inhibiting transforming growth factor-beta1 expression. Toxicol Appl Pharmacol. 2009;240(3):377–384.
  22. Jiang Y, Bao H, Ge Y, et al. Therapeutic targeting of GSK3β enhances the Nrf2 antioxidant response and confers hepatic cytoprotection in hepatitis C. Gut. 2015;64(1):168–179.
  23. Tanaka Y, Aleksunes LM, Yeager RL, et al. NF-E2-related factor 2 inhibits lipid accumulation and oxidative stress in mice fed a high-fat diet. J Pharmacol Exp Ther. 2008;325(2):655–664.
  24. Madison BB. Srebp2: A master regulator of sterol and fatty acid synthesis. J Lipid Res. 2016;57(3):333–335.
  25. Hayes JD, Dinkova-Kostova AT. The Nrf2 regulatory network provides an interface between redox and intermediary metabolism. Trends Biochem Sci. 2014;39(4):199–218.
  26. Perlemuter G, Sabile A, Letteron P, et al. Hepatitis C virus core protein inhibits microsomal triglyceride transfer protein activity and very low density lipoprotein secretion: A model of viral-related steatosis. FASEB J. 2002;16(2):185–194.
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