Selenizing astragalus polysaccharide attenuates PCV2 replication promotion caused by oxidative stress through autophagy inhibition via PI3K/AKT activation
Selenizing astragalus polysaccharide attenuates PCV2 replication promotion caused by oxidative stress through autophagy inhibition via PI3K/AKT activation
复制标题
硒黄芪多糖通过 PI3K/AKT 激活抑制自噬，从而减弱氧化应激引起的 PCV2 复制促进。
DOI：
10.1016/j.ijbiomac.2017.12.010
复制
发表时间：
2018-03-01
影响因子：
8.2
通讯作者：
Huang, Kehe
中科院分区：
文献类型：
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作者：
Liu, Dandan;Xu, Jing;Huang, Kehe
我们前期的研究表明，氧化应激可促进猪圆环病毒2型（PCV 2）的复制，黄芪多糖（APS）/硒可抑制PCV 2的复制。然而，硒化黄芪多糖（SAPS）是否对氧化应激诱导的PCV 2复制促进提供保护以及所涉及的机制尚不清楚。本研究旨在探讨氧化应激促进PCV 2复制的机制以及调控sAPS自噬的新的药理学途径。我们的研究结果表明，H2 O2通过3-甲基腺嘌呤（3-MA）和自噬相关基因5（ATG 5）的敲低增强自噬来促进PCV 2的复制。亚硒酸钠、APS、亚硒酸钠和APS的混合物以及sAPS分别显著抑制H2 O2诱导的PCV 2复制促进作用。其中sAPS的抑制作用最强。sAPS还能显著抑制H2 O2诱导的细胞自噬，增加Akt和mTOR的磷酸化水平。此外，特异性磷脂酰肌醇3-激酶/蛋白激酶B（PI 3 K/AKT）抑制剂LY 294002可显著减轻SAP对自噬和PCV 2复制的影响。总而言之，我们得出结论，H2 O2通过诱导自噬促进PCV 2复制，而sAPS通过PI 3 K/AKT激活抑制自噬来减弱PCV 2复制促进作用。(C)2017爱思唯尔B. V.保留所有权利。
Our previous studies have shown that oxidative stress could promote the porcine circovirus type 2 (PCV2) replication, and astragalus polysaccharide (APS)/selenium could suppress PCV2 replication. However, whether selenizing astragalus polysaccharide (SAPS) provides protection against oxidative stress-induced PCV2 replication promotion and the mechanism involved remain unclear. The present study aimed to explore the mechanism of the PCV2 replication promotion induced by oxidative stress and a novel pharmacotherapeutic approach involving the regulation of autophagy of sAPS. Our results showed that H2O2 promoted PCV2 replication via enhancing autophagy by using 3-methyladenine (3-MA) and autophagy-related gene 5 (ATG5) knockdown. Sodium selenite, APS, the mixture of sodium selenite and APS, and sAPS significantly inhibited H2O2-induced PCV2 replication promotion, respectively. Among these, sAPS exerted maximal inhibitory effect. sAPS could also significantly inhibit autophagy activated by H2O2 and increase the Akt and mTOR phosphorylation. Moreover, LY294002, the specific phosphoinositide 3-kinase/protein kinase B (PI3K/AKT) inhibitor, significantly alleviated the effects of SAPS on autophagy and PCV2 replication. Taken together, we conclude that H2O2 promotes PCV2 replication by inducing autophagy and sAPS attenuates the PCV2 replication promotion through autophagy inhibition via PI3K/AKT activation. (C) 2017 Elsevier B.V. All rights reserved.