Nogo-C regulates cardiomyocyte apoptosis during mouse myocardial infarction.
Nogo-C regulates cardiomyocyte apoptosis during mouse myocardial infarction.
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Nogo-C 调节小鼠心肌梗死期间心肌细胞凋亡
DOI：
10.1038/cddis.2016.331
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发表时间：
2016-10-20
影响因子：
9
通讯作者：
中科院分区：
文献类型：
--
作者：
心肌梗死是由于冠状动脉供血不足，导致心肌损伤，最终导致心力衰竭。心肌梗死（MI）和缺血相关心脏疾病中心肌细胞丢失的分子机制尚未完全清楚。Nogo-C是一种内质网蛋白，在包括心脏在内的组织中广泛表达，然而，Nogo-C的心脏功能仍然未知。在本研究中，我们发现Nogo-C在MI后的小鼠心脏中上调，并且缺氧处理也增加了心肌细胞中Nogo-C蛋白的水平。腺病毒介导的Nogo-C过表达导致心肌细胞凋亡，而通过shRNA敲低Nogo-C可保护心肌细胞免受缺氧诱导的细胞凋亡。重要的是，Nogo-C基因敲除小鼠在MI后表现出改善的心脏功能、较小的梗死面积和较少的凋亡细胞。此外，我们发现miR-182负调控Nogo-C表达，并在MI期间下调，在心肌细胞中表达miR-182保护缺氧和Nogo-C介导的细胞凋亡。我们的研究结果表明，增加心脏Nogo-C表达是缺血诱导的心肌细胞凋亡和心功能不全的充分和必要条件，这表明通过miRNA解除Nogo-C的调节可能是缺血相关心脏疾病的潜在治疗靶点。
Myocardial infarction is caused by insufficient coronary blood supply, which leads to myocardial damage and eventually the heart failure. Molecular mechanisms associated with the loss of cardiomyocytes during myocardial infarction (MI) and ischemia-related cardiac diseases are not yet fully understood. Nogo-C is an endoplasmic reticulum protein ubiquitously expressed in tissues including in the heart, however, the cardiac function of Nogo-C is still unknown. In the present study, we found that Nogo-C was upregulated in mouse hearts after MI, and hypoxic treatments also increased Nogo-C protein level in cardiomyocytes. Adenovirus mediated overexpression of Nogo-C led to cardiomyocyte apoptosis, whereas knockdown of Nogo-c by shRNA protected cardiomyocytes from hypoxia-induced cell apoptosis. Importantly, Nogo-C knockout mice displayed improved cardiac function, smaller infarct area, and less apoptotic cells after MI. Moreover, we found that miR-182 negatively regulated Nogo-C expression and was downregulated during MI, expressing miR-182 in cardiomyocytes protected hypoxia-and Nogo-C-mediated cell apoptosis. Our results indicate that increased cardiac Nogo-C expression is both sufficient and necessary for ischemia-induced cardiomyocyte apoptosis and cardiac dysfunction, suggesting that deregulation of Nogo-C by miRNA may be a potential therapeutic target for ischemia-related heart diseases.
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影响因子：
4.6
作者：
Li N;Hwangbo C;Jaba IM;Zhang J;Papangeli I;Han J;Mikush N;Larrivée B;Eichmann A;Chun HJ;Young LH;Tirziu D
通讯作者：
Tirziu D
DOI：
10.1073/pnas.1212655110
发表时间：
2013-02-05
影响因子：
11.1
作者：
Lumayag, Stephen;Haldin, Caroline E.;Xu, Shunbin
通讯作者：
Xu, Shunbin
影响因子：
3.4
作者：
Katz, Alison Rosamund
通讯作者：
Katz, Alison Rosamund
影响因子：
20.1
作者：
Gao E;Lei YH;Shang X;Huang ZM;Zuo L;Boucher M;Fan Q;Chuprun JK;Ma XL;Koch WJ
通讯作者：
Koch WJ
影响因子：
20.3
作者：
Di Lorenzo, Annarita;Manes, Thomas D.;Sessa, William C.
通讯作者：
Sessa, William C.