Endophilin A2 protects H2O2-induced apoptosis by blockade of Bax translocation in rat basilar artery smooth muscle cells
Endophilin A2 protects H2O2-induced apoptosis by blockade of Bax translocation in rat basilar artery smooth muscle cells
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Endophilin A2 通过阻断 Bax 易位保护 H2O2 诱导的大鼠基底动脉平滑肌细胞凋亡
DOI：
10.1016/j.yjmcc.2016.02.004
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发表时间：
2016-03-01
影响因子：
5
通讯作者：
Guan, Yong-Yuan
中科院分区：
文献类型：
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作者：
Liu, Yun;Gao, Min;Guan, Yong-Yuan
背景：细胞凋亡在维持正常细胞数量和组织稳态中起着核心作用。嗜内肽是一类进化上保守的蛋白，在胞吞作用中起着关键作用。在这里，我们确定了嗜内啡肽A2 （EndoII）是否参与过氧化氢（H2O2）诱导的大鼠基底动脉平滑肌细胞（BASMCs）凋亡及其潜在机制。方法和结果：通过小干扰RNA （siRNA）和EndoII过表达策略，我们发现EndoII siRNA敲低可降低细胞活力，促进H2O2诱导的细胞凋亡，表现为线粒体膜电位丧失，细胞色素c释放，caspase- 9,3和聚（adp -核糖）聚合酶（PARP）活化。而过表达EndoII则相反，可抑制h2o2诱导的BASMCs凋亡。进一步研究表明，EndoII与Bax之间存在直接相互作用。H2O2诱导凋亡后，EndoII与Bax的相关性显著降低，而Bax/tBid的相互作用增强，并伴有Bax从细胞质向线粒体的易位。敲低EndoII不影响Bax的表达，但进一步促进了Bax与tBid的结合，有利于Bax在线粒体的积累和Bax的活化；而过表达EndoII则产生相反的效果。此外，在h2o2处理的细胞中，EndoII siRNA表达增强，但EndoII过表达减轻，Bcl-2表达降低。结论：这些数据表明，EndoII可能通过抑制Bax对线粒体的定位来保护H2O2诱导的BASMCs凋亡。靶向EndoII可能是治疗细胞凋亡相关疾病的新策略。(C) 2016 Elsevier Ltd.版权所有。
Background: Apoptosis plays a central role in maintaining the normal cell number and tissue homeostasis. Endophilins are a family of evolutionarily conserved proteins that have the critical role in endocytosis. Here, we determined whether endophilin A2 (EndoII) contributes to hydrogen peroxide (H2O2)-induced apoptosis in rat basilar artery smooth muscle cells (BASMCs) and the underlying mechanisms.Methods and results: By using small interference RNA (siRNA) and EndoII overexpression strategy, we found that EndoII siRNA knockdown reduced cell viability and promoted H2O2 -induced cell apoptosis, evidenced by loss of mitochondria] membrane potential, release of cytochrome c, and activation of caspase-9, 3 and poly (ADP-ribose) polymerase (PARP). In contrast, EndoII overexpression showed opposite effects and inhibited H2O2-induced BASMCs apoptosis. Further studies revealed that there was a direct interaction between EndoII and Bax. Upon H2O2 -induced apoptosis, the association of EndoII with Bax were significantly decreased, while the interaction of Bax/tBid were increased, accompanied by a translocation of Bax from cytosol to mitochondria. Knockdown of EndoII did not affect the expression of Bax, but further promoted the binding of Bax with tBid and favored the accumulation of Bax to mitochondria as well as Bax activation; whereas EndoII overexpression produced the opposite effects. In addition, EndoII siRNA aggravated, but EndoII overexpression alleviated, the reduction of Bcl-2 expression in H2O2-treated cells.Conclusions: These data suggested a role of EndoII in protecting BASMCs apoptosis induced by H2O2, possibly by inhibiting the addressing of Bax to mitochondria. Targeting on EndoII may be a new strategy to treat apoptosis-associated diseases. (C) 2016 Elsevier Ltd. All rights reserved.