TOM7 silencing exacerbates focal cerebral ischemia injury in rat by targeting PINK1/Beclin1-mediated autophagy
TOM7 silencing exacerbates focal cerebral ischemia injury in rat by targeting PINK1/Beclin1-mediated autophagy
复制标题
TOM7沉默通过靶向PINK1/Beclin1介导的自噬加剧大鼠局灶性脑缺血损伤
DOI：
10.1016/j.bbr.2018.11.031
复制
发表时间：
2019-03-15
影响因子：
2.7
通讯作者：
Zhao Yong
中科院分区：
文献类型：
--
作者：
Jiang Ning;Tan Junyi;Zhao Yong
激活的自噬在包括局灶性脑缺血损伤在内的脑血管疾病中被广泛观察到，但其分子机制尚不清楚。TOM7是线粒体膜外膜(TOM)复合体蛋白转位酶的一个组成部分，可能调节TOM复合体的组装。然而，对TOM7如何影响脑缺血损伤的了解有限。在这项研究中，我们证明了TOM7的表达在大鼠光栓性脑缺血模型后上调，在3天时达到峰值。此外，TOM7基因敲除可能加重脑缺血损伤，抑制缺血性卒中后的自噬。TOM7在机制上可能通过PINK1/Beclin1通路调节脑缺血损伤后的自噬。这些结果表明，TOM7沉默可能通过抑制PINK1/Beclin1途径介导的自噬而加重脑缺血损伤。
Activated autophagy has been intensively observed in cerebrovascular diseases, including focal cerebral ischemia injury, but its molecular mechanisms remain unclear. TOM7, which is a component of the protein translocase of the outer mitochondrial membrane (TOM) complex, may modulate assembly of the TOM complex. However, an understanding of how TOM7 affects cerebral ischemia injury is limited. In this study, we demonstrate that the expression of TOM7 is up-regulated after a photothrombotic cerebral ischemic model in rats, peaking at 3 days. In addition, TOM7 knockdown may aggravate cerebral ischemic injury and inhibit autophagy after ischemic stroke. Mechanically, TOM7 may regulate autophagy through the PINK1/Beclin1 pathway after cerebral ischemia injury. These results demonstrate that TOM7 silencing may aggravate cerebral ischemia injury through inhibiting PINK1/Beclin1 pathway-mediated autophagy.