The role S-nitrosylation in manganese-induced autophagy dysregulation in SH-SY5Y cells
The role S-nitrosylation in manganese-induced autophagy dysregulation in SH-SY5Y cells
复制标题
S-亚硝基化在锰诱导的 SH-SY5Y 细胞自噬失调中的作用
DOI：
10.1002/tox.22457
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发表时间：
2017-12-01
影响因子：
4.5
通讯作者：
Xu, Bin
中科院分区：
文献类型：
--
作者：
Ma, Zhuo;Wang, Can;Xu, Bin
Overexposure to manganese (Mn) has been known to induce nitrosative stress. The dysregulation of autophagy has implicated in nitric oxide (NO) bioactivity alterations. However, the mechanism of Mn-induced autophagic dysregulation is unclear. The protein of Bcl-2 was considered as a key role that could participate to the autophagy signaling regulation. To further explore whether S-nitrosylation of Bcl-2 involved in Mn-induced autophagy dysregulation, we treated human neuroblastoma (SH-SY5Y) cells with Mn and pretreated cells with 1400 W, a selective iNOS inhibitor. After cells were treated with 400 M Mn for 24 h, there were significant increases in production of NO, inducible NO synthase (iNOS) activity, the mRNA and protein expressions of iNOS. Interestingly, autophagy was activated after cells were treated with Mn for 0-12 h; while the degradation process of autophagy-lysosome pathway was blocked after cells were treated with Mn for 24 h. Moreover, S-nitrosylated JNK and Bcl-2 also increased and phospho-JNK and phospho-Bcl-2 reduced in Mn-treated cells. Then, the affinity between Bcl-2 and Beclin-1 increased significantly in Mn-treated cells. We used the 1400 W to neutralize Mn-induced nitrosative stress. The results showed that S-nitrosylated JNK and Bcl-2 reduced while their phosphorylation were recovered to some extent. The findings revealed that NO-mediated S-nitrosylation of Bcl-2 directly affected the interaction between Beclin-1 and Bcl-2 leading to autophagy inhibition.
