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谷氧还蛋白1(glutaredoxin 1,Grx1)作为一种重要的抗氧化剂,通过响应多种重要蛋白质的活动和功能调节细胞的关键过程.了解Grx1功能,对寻求糖尿病和心肌病等,以凋亡失调和氧化还原稳态改变为发病机制的疾病的新颖治疗策略至关重要.为研究Grx1对高糖诱导的大鼠心肌细胞凋亡的抑制作用及相关信号机制,本研究以高糖诱导大鼠心肌细胞H9c2建立高糖损伤模型,采用免疫印迹实验检测caspase-3、8、9蛋白活性片段的表达和凋亡信号蛋白JNK/c-Jun的磷酸化水平.结果显示,与正常对照组相比,高糖组caspase家族中,剪切的caspase-3、caspase-8、caspase-9相对含量均显著增多,JNK和c-Jun蛋白的磷酸化水平均显著上调.但给予外源性Grx1保护后,剪切的caspase-3和caspase-8相对含量均显著降低,JNK和c-Jun蛋白的磷酸化水平均显著下调.上述结果表明,高糖通过介导caspase-8/3和caspase-9/3凋亡通路,并激活凋亡相关信号通路JNK/c-Jun诱导H9c2心肌细胞凋亡.给予外源性Grx1保护后,可通过抑制caspase-8/3凋亡通路和JNK/c-Jun信号通路的激活,拮抗高糖诱导的心肌细胞凋亡.
As an important antioxidant, glutaredoxin 1 (Grx1) regulates key cellular processes by responding to the activities and functions of a variety of important proteins, understanding the function of Grx1, and seeking for signs of diabetes and cardiomyopathy to apoptosis In order to study the inhibitory effect of Grx1 on cardiomyocyte apoptosis induced by high glucose and related signaling mechanisms, we used high glucose-induced rat H9c2 cells were cultured with high glucose, and the expression of active caspase-3, 8 and 9 protein and the phosphorylation level of JNK / c-Jun protein were detected by Western blotting.The results showed that compared with the normal control group , The relative contents of cleaved caspase-3, caspase-8 and caspase-9 in caspase family were significantly increased, and the phosphorylation levels of JNK and c-Jun protein were significantly increased in high glucose group, but after exogenous Grx1 protection , The relative content of cleaved caspase-3 and caspase-8 were significantly decreased, and the phosphorylation levels of JNK and c-Jun protein were significantly down-regulated.The above results showed that high glucose could induce caspase-8/3 and caspase-9 / 3 apoptotic pathway and activate apoptosis JNK / c-Jun can induce cardiomyocyte apoptosis in H9c2 cells.Exogenous Grx1 can protect cells against apoptosis by inhibiting the activation of caspase-8/3 and JNK / c-Jun signaling pathways Myocardial cell apoptosis.