Pim-2 protects H9c2 cardiomyocytes from hypoxia/reoxygenation-induced apoptosis via downregulation of Bim expression.
Pim-2 protects H9c2 cardiomyocytes from hypoxia/reoxygenation-induced apoptosis via downregulation of Bim expression.
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DOI：
10.1016/j.etap.2016.10.011
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发表时间：
2016-12
影响因子：
4.3
通讯作者：
Yan Xu;Yawei Xing;Yanjie Xu;Cha-hua Huang;H. Bao;K. Hong;Xiaoshu Cheng
中科院分区：
文献类型：
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作者：
Yan Xu;Yawei Xing;Yanjie Xu;Cha-hua Huang;H. Bao;K. Hong;Xiaoshu Cheng
我们知道，沉默Bim，促凋亡蛋白，显着减弱葡萄糖和缺氧诱导的心肌细胞凋亡。然而，心脏中Bim激活的调节机制仍然未知。Pim-2是被认为参与细胞存活和增殖的三个Pim丝氨酸/苏氨酸激酶家族成员之一。H9 c2心肌细胞在体外经受缺氧/复氧（H/R）条件，模拟体内缺血/再灌注损伤。H/R可增加Bim、Cyt C和Pim-2的表达，诱导H9 c2细胞凋亡。Pim-2过表达通过下调Bim和Cyt C的表达来减弱H/R诱导的H9 c2细胞凋亡。Pim-2的沉默通过上调Bim和Cyt C表达促进H/R诱导的细胞凋亡。Co-IP分析显示Pim-2与Bim蛋白相互作用，Bim Ser 65被Pim-2磷酸化。MG 132阻断蛋白酶体活性可抑制Bim降解，Bim S65 A突变可逆转Pim-2抗H/R诱导的细胞凋亡作用。这些数据表明，Pim-2是一种新的Bim相互作用蛋白，负调控Bim降解和保护H9 c2心肌细胞免受H/R诱导的凋亡。
We know that silencing Bim, a pro-apoptosis protein, significantly attenuates glucose and oxygen-deprived induced apoptosis in cardiomyocytes. However, the mechanisms underlying the regulation of the Bim activation in the heart have remained unknown. Pim-2 is one of three Pim serine/threonine kinase family members thought to be involved in cell survival and proliferation. H9c2 cardiomyocytes were subjected to a hypoxia/reoxygenation (H/R) condition in vitro, mimicking ischemic/reperfusion injury in vivo. H/R augmented the expression of Bim, Cyt C, and Pim-2 and induced H9c2 cell apoptosis. Overexpression of Pim-2 attenuated apoptosis which induced by H/R in H9c2 cells, via downregulation of Bim and Cyt C expression. Silencing of Pim-2 promoted H/R-induced apoptosis via upregulation of Bim and Cyt C expression. Co-IP revealed the interaction between Pim-2 and Bim protein, with Bim Ser65phosphorylated by Pim-2. Furthermore, blocking proteasome activity by MG132 prevented Bim degradation, and Bim S65A mutation could reverse the anti-apoptotic role of Pim-2 which induced by H/R. These data demonstrated that Pim-2 is a novel Bim-interacting protein, which negatively regulates Bim degradation and protects H9c2 cardiomyocytes from H/R-induced apoptosis.