The effect of mycophenolic acid on expression of autophagy-related genes in hepatocytes

JIANG Jun-jun; SU Jin-ming; LI Yu; CHEN Hui; LIANG Bing-yu; HUANG Jie-gang; PAN Pei-jiang; LIU Jie; ZHAO Fang-ning; LIANG Hao; HUO Wen-zhe; YE Li

doi:10.16462/j.cnki.zhjbkz.2016.03.008

Volume 20 Issue 3

Mar. 2016

Turn off MathJax

Article Contents

Article Navigation > CHINESE JOURNAL OF DISEASE CONTROL & PREVENTION > 2016 > 20(3): 244-248

JIANG Jun-jun, SU Jin-ming, LI Yu, CHEN Hui, LIANG Bing-yu, HUANG Jie-gang, PAN Pei-jiang, LIU Jie, ZHAO Fang-ning, LIANG Hao, HUO Wen-zhe, YE Li. The effect of mycophenolic acid on expression of autophagy-related genes in hepatocytes[J]. CHINESE JOURNAL OF DISEASE CONTROL & PREVENTION, 2016, 20(3): 244-248. doi: 10.16462/j.cnki.zhjbkz.2016.03.008

Citation:

JIANG Jun-jun, SU Jin-ming, LI Yu, CHEN Hui, LIANG Bing-yu, HUANG Jie-gang, PAN Pei-jiang, LIU Jie, ZHAO Fang-ning, LIANG Hao, HUO Wen-zhe, YE Li. The effect of mycophenolic acid on expression of autophagy-related genes in hepatocytes[J]. CHINESE JOURNAL OF DISEASE CONTROL & PREVENTION, 2016, 20(3): 244-248. doi: 10.16462/j.cnki.zhjbkz.2016.03.008

Citation:

JIANG Jun-jun, SU Jin-ming, LI Yu, CHEN Hui, LIANG Bing-yu, HUANG Jie-gang, PAN Pei-jiang, LIU Jie, ZHAO Fang-ning, LIANG Hao, HUO Wen-zhe, YE Li. The effect of mycophenolic acid on expression of autophagy-related genes in hepatocytes[J]. CHINESE JOURNAL OF DISEASE CONTROL & PREVENTION, 2016, 20(3): 244-248. doi: 10.16462/j.cnki.zhjbkz.2016.03.008

PDF( 1092 KB)

The effect of mycophenolic acid on expression of autophagy-related genes in hepatocytes

doi: 10.16462/j.cnki.zhjbkz.2016.03.008

1. Guangxi Medical University, Guangxi Key Laboratory of AIDS Prevention and Research & School of Public Health, Nanning 530021, China;
2. Geriatrics Digestion Department of Internal Medicine, the First Affiliated Hospital of GuangXi Medical University, Nanning 530021, China;
3. Wuhan University Center for Animal Experiment/ABSL-3 Lab, Wuhan 430000, China

Received Date: 2015-11-04
Rev Recd Date: 2016-01-02

Abstract

Abstract

Objective To investigate the effect of mycophenolic acid (MPA) on hepatitis C virus (HCV) replkication and the expression of autophagy-related genes treated by MPA in HCV JFH-1 infected Huh7 cells. Methods Huh7 cells were infected with hepatitis C virus Japanese fulminant hepatitis -1(HCV JFH-1), and then treated with 5μg/ml MPA for 24h. The treated cells were collected to detect the expression of HCV, microtubule-associated protein 1 light chain(LC3B), autophagy-related gene 3(ATG3) and autophagy-related gene 7(ATG7) at messenger ribonucleic acid (mRNA) and protein levels by real-time quantitative PCR(qPCR) and Western blot assay respectively. Results MPA treatment decreased the expression of HCV and LC3B mRNA and LC3B-II protein (P<0.001, compared with control group), and reduced the expression of ATG3 and ATG7 at mRNA and protein levels (P<0.001, P=0.003; P=0.010, P=0.002 compared with control group). Conclusions MPA treatment could inhibit HCV replication and block autopahgy by down-regulating the expression of ATG3 and ATG7. These results suggest that MPA has a potent antiviral ability against HCV replication by blocking cellular autophagy.
- Mycophenolic acid,
- Autophagy,
- Hepatitis C

FullText(HTML)

References(20)

References

Limaye AR, Firpi RJ. Management of recurrent hepatitis C infection after liver transplantation [J]. Clin Liver Dis, 2011,15(4):845-858.

Pillai AA, Levitsky J. Overview of immunosuppression in liver transplantation [J]. World J Gastroenterol, 2009,15(34):4225-4233.

Henry SD, Metselaar HJ, Lonsdale RC, et al. Mycophenolic acid inhibits hepatitis C virus replication and acts in synergy with cyclosporin A and interferon-alpha [J]. Gastroenterology, 2006,131(5):1452-1462.

Dreux M, Chisari FV. Impact of the autophagy machinery on hepatitis C virus infection [J]. Viruses, 2011,3(8):1342-1357.

Dreux M, Gastaminza P, Wieland SF, et al. The autophagy machinery is required to initiate hepatitis C virus replication [J]. Proc Natio Acad Sci U S A, 2009,106(33):14046-14051.

Tanida I, Fukasawa M, Ueno T, et al. Knockdown of autophagy-related gene decreases the production of infectious hepatitis C virus particles [J]. Autophagy, 2009,5(7):937-945.

Khakpoor A, Panyasrivanit M, Wikan N, et al. A role for autophagolysosomes in dengue virus 3 production in HepG2 cells [J].J Gen Virol, 2009,90(Pt 5):1093-1103.

Manzia TM, Angelico R, Ciano P, et al. Impact of immunosuppression minimization and withdrawal in long-term hepatitis C virus liver transplant recipients [J]. World J Gastroenterol, 2014,20(34):12217-12225.

Manrique A, Jimenez C, Ortega P, et al. Mycophenolate mofetil monotherapy in patients who underwent liver transplantation for hepatitis C cirrhosis [J]. Transplantat Proc, 2008,40(9):2962-2964.

Ye L, Li J, Zhang T, et al. Mycophenolate mofetil inhibits hepatitis C virus replication in human hepatic cells [J]. Virus Res, 2012,168(1-2):33-40.

Zekry A, Gleeson M, Guney S, et al. A prospective cross-over study comparing the effect of mycophenolate versus azathioprine on allograft function and viral load in liver transplant recipients with recurrent chronic HCV infection [J]. Liver Transpl, 2004,10(1):52-57.

Kornberg A, Kupper B, Tannapfel A, et al. Impact of mycophenolate mofetil versus azathioprine on early recurrence of hepatitis C after liver transplantation [J]. Int Immunopharmacol, 2005,5(1):107-115.

Kabeya Y, Mizushima N, Ueno T, et al. LC3, a mammalian homologue of yeast Apg8p, is localized in autophagosome membranes after processing [J]. EMBO J, 2000,19(21):5720-5728.

Tanida I, Ueno T, Kominami E. LC3 conjugation system in mammalian autophagy [J].Int J Biochemi Cell Biol, 2004,36(12):2503-2518.

Jordan TX, Randall G. Manipulation or capitulation: virus interactions with autophagy [J]. Microbes Infect, 2012,14(2):126-139.

McCoy F, Hurwitz J, McTavish N, et al. Obatoclax induces Atg7-dependent autophagy independent of beclin-1 and BAX/BAK [J]. Cell Death Dis, 2010,1:e108.

Sir D, Kuo CF, Tian Y, et al. Replication of hepatitis C virus RNA on autophagosomal membranes [J]. J Biol Chem, 2012,287(22):18036-18043.

Shrivastava S, Raychoudhuri A, Steele R, et al. Knockdown of autophagy enhances the innate immune response in hepatitis C virus-infected hepatocytes [J]. Hepatology, 2011,53(2):406-414.

Kaiser SE, Mao K, Taherbhoy AM, et al. Noncanonical E2 recruitment by the autophagy E1 revealed by Atg7-Atg3 and Atg7-Atg10 structures [J]. Nat Struct Mol Biol, 2012,19(12):1242-1249.

Wang J, Whiteman MW, Lian H, et al. A non-canonical MEK/ERK signaling pathway regulates autophagy via regulating Beclin 1 [J]. J Biol Chem, 2009,284(32):21412-21424.

Relative Articles

Supplements(0)

Cited By

Proportional views