Corin 通过 PI3K/AKT 和 NF-κB 通路保护心肌细胞中的 HO 诱导的细胞凋亡。
Corin protects HO-induced apoptosis through PI3K/AKT and NF-κB pathway in cardiomyocytes.
机构信息
Department of Cardiology, Shanghai Songjiang District Center Hospital, Shanghai 201600, China; Department of Cardiology, Seventh People's Hospital of Shanghai University of TCM, Shanghai 200137, China.
Department of Cardiology, Seventh People's Hospital of Shanghai University of TCM, Shanghai 200137, China.
出版信息
Biomed Pharmacother. 2018 Jan;97:594-599. doi: 10.1016/j.biopha.2017.10.090. Epub 2017 Nov 6.
BACKGROUND
The functional role of corin in HO-induced apoptosis is largely unexplored. The present study investigated the protective role of corin against cell injury by possible involvement of PI3K/AKT and NF-kB signaling pathways in cardiomyocytes.
METHOD
Cardiomyocytes H9c2 and HL-1 cells were used in the study. Cell viability was measured using CCK-8 assay; cell apoptosis was analyzed by flow cytometry, TUNEL assay, and western blot; and cell migration was measured using wound healing assay. The fluorescent intensities of reactive oxygen species (ROS) were measured using a flow cytometer. Quantitative RT-PCR was used to measure the mRNA expression of corin. Western blot was used to measure the protein expression of corin, apoptosis-related proteins (Bax, cleaved-Caspase-3 and -9), and PI3K/AKT and NF-κB signaling pathway proteins.
RESULTS
Treatment with HO (150μM, 6h) significantly decreased cell viability and relative migration, increased apoptosis, and decreased the expression of corin in H9c2 and HL-1 cells. Overexpression of corin alleviated the HO-induced cell injury by increasing cell viability and migration and decreasing apoptosis in the cardiomyocytes. Overexpression of corin also decreased the ROS level in the cardiomyocytes likely through upregulating HIF-1α. These effects of corin on the cell injury might be mediated via the corin-induced activations of PI3K/AKT and NF-κB signaling pathways.
CONCLUSION
Overexpression of corin protected cardiomyocytes from HO-induced injury by decreasing apoptosis and ROS level via activations of the PI3K/AKT and NF-κB signaling pathways and upregulating HIF-1α.
背景
心钠肽原酶（corin）在 HO 诱导的细胞凋亡中的功能作用在很大程度上仍未被探索。本研究通过可能涉及的 PI3K/AKT 和 NF-κB 信号通路，研究了 corin 在心肌细胞中对抗细胞损伤的保护作用。
方法
本研究使用 H9c2 和 HL-1 心肌细胞。通过 CCK-8 测定法测量细胞活力；通过流式细胞术、TUNEL 测定法和 Western blot 分析细胞凋亡；通过划痕愈合测定法测量细胞迁移。使用流式细胞仪测量活性氧（ROS）的荧光强度。使用定量 RT-PCR 测量 corin 的 mRNA 表达。Western blot 用于测量 corin、凋亡相关蛋白（Bax、裂解型 Caspase-3 和 -9）以及 PI3K/AKT 和 NF-κB 信号通路蛋白的蛋白表达。
结果
用 150μM HO（6h）处理后，H9c2 和 HL-1 细胞的细胞活力和相对迁移率显著降低，凋亡增加，corin 的表达降低。corin 的过表达通过增加心肌细胞的活力和迁移，减少凋亡，缓解了 HO 诱导的细胞损伤。corin 的过表达还可能通过上调 HIF-1α 降低心肌细胞中的 ROS 水平。corin 对细胞损伤的这些影响可能是通过 corin 诱导的 PI3K/AKT 和 NF-κB 信号通路的激活介导的。
结论
corin 的过表达通过激活 PI3K/AKT 和 NF-κB 信号通路并上调 HIF-1α，降低了细胞凋亡和 ROS 水平，从而保护心肌细胞免受 HO 诱导的损伤。
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