Autophagy is involved in the protective effect of endophilin A2 on H2O2-induced apoptosis in H9C2 cardiomyocytes
Autophagy is involved in the protective effect of endophilin A2 on H2O2-induced apoptosis in H9C2 cardiomyocytes
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自噬参与内皮素 A2 对 H2O2 诱导的 H9C2 心肌细胞凋亡的保护作用
DOI：
10.1016/j.bbrc.2018.03.151
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发表时间：
2018-05-05
影响因子：
3.1
通讯作者：
Luo, Jian-Dong
中科院分区：
文献类型：
--
作者：
Liu, Yun;Liu, Hai-Qi;Luo, Jian-Dong
细胞凋亡在正常胚胎发育和组织稳态调节中起着关键作用。EndoA 2（EndoA 2）被广泛报道调节内吞作用。此外，已证实EndoA 2参与肿瘤转移、神经调节和血管功能。本研究采用siRNA和Ad-EndoA 2转染策略，探讨EndoA 2对H2 O2诱导的H9 C2心肌细胞凋亡的保护作用及其机制。我们发现，EndoA 2 siRNA敲低促进H9 C2心肌细胞中H2 O2诱导的凋亡，表现为细胞数量减少，凋亡细胞增加和caspase-3活化。相反，EndoA 2过表达表现出相反的效果，并抑制H2 O2诱导的H9 C2心肌细胞凋亡。进一步的研究表明，EndoA 2过表达增强自噬，表现为LC 3 II/I比率增加和P62降解，而EndoA 2 siRNA敲低产生相反的效果。此外，我们发现Bif-1和Beclin-1之间存在相互作用。H2 O2处理后，Bif-1和Beclin-1的结合显著增强。EndoA 2过表达进一步促进了Bif-1与Beclin-1的结合，而EndoA 2 siRNA敲低则降低了这种结合。这些数据有力地表明，EndoA 2抑制H2 O2诱导的H9 C2心肌细胞凋亡，可能是通过促进Bif-1与Beclin-1形成复合物并加强自噬。这项研究为心脏疾病提供了一个新的靶点。(C)2018由Elsevier Inc.出版
Apoptosis plays a critical role in normal embryonic development and tissue homeostasis regulation. EndophilinA2 (EndoA2) is widely reported to regulate endocytosis. Additionally, EndoA2 has been demonstrated to be involved in tumor metastasis, neuroregulation and vascular function. In this study, we used siRNA and Ad-EndoA2 transfection strategy to investigate whether EndoA2 provides a protective effect against apoptosis induced by H2O2 in H9C2 cardiomyocytes and the underlying mechanisms. We found that EndoA2 siRNA knockdown promoted H2O2-induced apoptosis in H9C2 cardiomyocytes, evidenced by decreased cell number, increased apoptotic cells, and activation of caspase-3. In contrast, EndoA2 overexpression showed the opposite effects and inhibited H2O2-induced apoptosis in H9C2 cardiomyocytes. Further studies revealed that EndoA2 overexpression strengthened autophagy, evidenced by the increased LC3 II/I ratio and P62 degradation, whereas EndoA2 siRNA knockdown produced the opposite effects. Furthermore, we revealed that there was an interaction between Bif-1 and Beclin-1. Upon H2O2 treatment, the association of Bif-1 and Beclin-1 remarkably increased. EndoA2 overexpression further promoted the binding of Bif-1 with Beclin-1, whereas EndoA2 siRNA knockdown reduced this association. These data strongly suggested that EndoA2 inhibited H2O2 induced apoptosis in H9C2 cardiomyocytes, possibly by promoting Bif-1 to form a complex with Beclin-1 and strengthening autophagy. This study provides a novel target for heart diseases. (C) 2018 Published by Elsevier Inc.