Mitochonic acid 5 regulates mitofusin 2 to protect microglia

作     者：Jian Tan Shuang-Xi Chen Qing-Yun Lei Shan-Qing Yi Na Wu Yi-Lin Wang Zi-Jian Xiao Heng Wu Jian Tan;Shuang-Xi Chen;Qing-Yun Lei;Shan-Qing Yi;Na Wu;Yi-Lin Wang;Zi-Jian Xiao;Heng Wu

作者机构：Department of NeurologyThe First Affiliated Hospital of University of South ChinaHengyangHunan ProvinceChina 

出 版 物：《Neural Regeneration Research》 (中国神经再生研究（英文版）)

年 卷 期：2021年第16卷第9期

页      面：1813-1820页

核心收录：

学科分类：0710[理学-生物学] 07[理学] 071006[理学-神经生物学] 

基　　金：supported by the Natural Science Foundation of Hunan Province of China No.2017JJ3273(to ZJX) 

主　　题：apoptosis autophagy related 5 Beclin1 BV-2 cells caspase-3 inflammation lipopolysaccharide mitophagy Smac survival 

摘      要：Microglial apoptosis is associated with neuroinflammation and no effective strategies are currently available to protect microglia against inflammation-induced apoptosis. Mouse microglial BV-2 cells(5 × 10^6) were incubated with 10 μg/mL lipopolysaccharides for 12 hours to mimic an inflammatory environment. Then the cells were co-cultured with mitochonic acid 5(MA-5) for another 12 hours. MA-5 improved the survival of lipopolysaccharide-exposed cells. MA-5 decreased the activity of caspase-3, which is associated with apoptosis. MA-5 reduced the number of terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling-positive cells, and increased adenosine triphosphate levels in cells. MA-5 decreased the open state of the mitochondrial permeability transition pore and reduced calcium overload and diffusion of second mitochondria-derived activator of caspase(Smac). MA-5 decreased the expression of apoptosis-related proteins(mitochondrial Smac, cytoplasmic Smac, pro-caspase-3, cleaved-caspase-3, and caspase-9), and increased the levels of anti-apoptotic proteins(Bcl2 and X-linked inhibitor of apoptosis protein), mitochondria-related proteins(mitochondrial fusion protein 2, mitochondrial microtubule-associated proteins 1 A/1 B light chain 3 B II), and autophagy-related proteins(Beclin1, p62 and autophagy related 5). However, MA-5 did not promote mitochondrial homeostasis or decrease microglial apoptosis when Mitofusin 2 expression was silenced. This shows that MA-5 increased Mitofusin 2-related mitophagy, reversed cellular energy production and maintained energy metabolism in BV-2 cells in response to lipopolysaccharide-induced inflammation. These findings indicate that MA-5 may promote the survival of microglial cells via Mitofusin 2-related mitophagy in response to lipopolysaccharide-induced inflammation.