AGK2，一种SIRT2抑制剂，可抑制体外和体内乙型肝炎病毒的复

StephenW

Int J Med Sci. 2018 Sep 7;15(12):1356-1364. doi: 10.7150/ijms.26125. eCollection 2018.
AGK2, A SIRT2 Inhibitor, Inhibits Hepatitis B Virus Replication In Vitro And In Vivo.
Yu HB1, Jiang H1, Cheng ST1, Hu ZW1, Ren JH1, Chen J1.
Author information

1
    Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), The Second Affiliated Hospital, Chongqing Medical University, Chongqing, China.

Abstract

Sirtuin 2 (SIRT2) is a nicotinamide adenine dinucleotide (NAD +)-dependent class III histone deacetylase. We have reported that HBx (hepatitis B virus X protein)-elevated SIRT2 promotes HBV replication and hepatocarcinogenesis. However, the potential anti-HBV effect of AGK2, a selective inhibitor of SIRT2, has not been reported. Here, the role of AGK2 on HBV replication was examined in the HepAD38 and HepG2-NTCP cell lines. The HBV genome was stably integrated in HepAD38 cell line which expresses HBV under the control of tetracycline. The HepG2-NTCP cells expressing the sodium taurocholate cotransporting polypeptide (NTCP) receptor are susceptible to HBV infection. We found that AGK2 exhibited a robust anti-HBV activity with minimal hepatotoxicity. AGK2 inhibited the expression of HBV total and 3.5kb RNAs, DNA replicative intermediates and HBV core protein (HBc). Moreover, AGK2 treatment suppressed the secretion of the hepatitis B e antigen (HBeAg) and hepatitis B surface antigen (HBsAg). Importantly, AGK2 treatment inhibited serum HBV DNA, HBeAg and HBsAg levels as well as hepatic HBV DNA, RNA and HBc in the HBV transgenic mice. The results indicated that AGK2, as a SIRT2 inhibitor, might be a new therapeutic option for controlling HBV infection.
KEYWORDS:

AGK2; HBV; SIRT2

PMID:
    30275764
PMCID:
    PMC6158674
DOI:
    10.7150/ijms.26125

StephenW

Int J Med Sci。 2018年9月7日; 15（12）：1356-1364。 doi：10.7150 / ijms.26125。 eCollection 2018。
AGK2，一种SIRT2抑制剂，可抑制体外和体内乙型肝炎病毒的复制。
Yu HB1，Jiang H1，Cheng ST1，Hu ZW1，Ren JH1，Chen J1。
作者信息

1
    重庆医科大学附属第二医院传染病分子生物学教育部重点实验室，重庆

抽象

Sirtuin 2（SIRT2）是一种烟酰胺腺嘌呤二核苷酸（NAD +） - 依赖的III类组蛋白去乙酰化酶。我们已经报道HBx（乙型肝炎病毒X蛋白）升高的SIRT2促进HBV复制和肝癌发生。然而，尚未报道AGK2（一种SIRT2的选择性抑制剂）的潜在抗HBV作用。在此，在HepAD38和HepG2-NTCP细胞系中检查了AGK2对HBV复制的作用。 HBV基因组稳定整合到HepAD38细胞系中，该细胞系在四环素控制下表达HBV。表达牛磺胆酸钠协同转运多肽（NTCP）受体的HepG2-NTCP细胞对HBV感染敏感。我们发现AGK2表现出强大的抗HBV活性，具有最小的肝毒性。 AGK2抑制HBV总RNA和3.5kb RNAs，DNA复制中间体和HBV核心蛋白（HBc）的表达。此外，AGK2处理抑制了乙型肝炎e抗原（HBeAg）和乙型肝炎表面抗原（HBsAg）的分泌。重要的是，AGK2处理抑制HBV转基因小鼠中的血清HBV DNA，HBeAg和HBsAg水平以及肝HBV DNA，RNA和HBc。结果表明，作为SIRT2抑制剂的AGK2可能是控制HBV感染的新治疗选择。
关键词：

AGK2; HBV; SIRT2

结论：
    30275764
PMCID：
    PMC6158674
DOI：
    10.7150 / ijms.26125

StephenW

http://www.medsci.org/v15p1356.htm

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