Departments of Anesthesiology, SUNY Downstate Health Science University, 450 Clarkson Avenue, Brooklyn, NY 11203, USA.
Quantitative Proteomics and Metabolomics Center, Department of Biological Sciences, Columbia University, New York, NY 10027, USA.
Cells. 2023 Sep 15;12(18):2282. doi: 10.3390/cells12182282.
Myocardial ischemia/reperfusion (I/R) elicits an acute inflammatory response involving complement factors. Recently, we reported that myocardial necrosis was decreased in complement C3 mice after heart I/R. The current study used the same heart model to test the effect of C3 on myocardial apoptosis and investigated if C3 regulation of apoptosis occurred in human cardiomyocytes. Comparative proteomics analyses found that cytochrome c was present in the myocardial C3 complex of WT mice following I/R. Incubation of exogenous human C3 reduced apoptosis in a cell culture system of human cardiomyocytes that did not inherently express C3. In addition, human C3 inhibited the intrinsic apoptosis pathway in a cell-free apoptosis system. Finally, human pro-C3 was found to bind with an apoptotic factor, pro-caspase 3, in a cell-free system. Thus, we present firsthand evidence showing that C3 readily reduces myocardial apoptosis via interaction with the intrinsic apoptotic pathway.
心肌缺血/再灌注（I/R）会引发涉及补体因子的急性炎症反应。最近，我们报道了补体 C3 敲除小鼠的心肌 I/R 后心肌坏死减少。本研究使用相同的心脏模型来测试 C3 对心肌细胞凋亡的影响，并研究 C3 是否调节人心肌细胞的凋亡。比较蛋白质组学分析发现，WT 小鼠的心肌 C3 复合物在 I/R 后存在细胞色素 c。在不固有表达 C3 的人心肌细胞的细胞培养系统中，外源性人 C3 减少了细胞凋亡。此外，人 C3 在无细胞凋亡系统中抑制内在凋亡途径。最后，在无细胞系统中发现人原 C3 与人凋亡因子原胱天蛋白酶 3 结合。因此，我们首次提供了直接证据，表明 C3 通过与内在凋亡途径相互作用，很容易减少心肌细胞凋亡。
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