Prohibitin overexpression improves myocardial function in diabetic cardiomyopathy.
Prohibitin overexpression improves myocardial function in diabetic cardiomyopathy.
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抑制素过度表达可改善糖尿病心肌病的心肌功能
DOI：
10.18632/oncotarget.6384
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发表时间：
2016-01-05
期刊：
影响因子：
--
通讯作者：
Zhang MX
中科院分区：
文献类型：
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作者：
Dong WQ;Chao M;Lu QH;Chai WL;Zhang W;Chen XY;Liang ES;Wang LB;Tian HL;Chen YG;Zhang MX
抑制素 (PHB) 是一种高度保守的蛋白质，涉及多种细胞功能，包括增殖、凋亡、肿瘤抑制、转录和线粒体蛋白质折叠。然而，其在糖尿病心肌病（DCM）中的作用仍不清楚。在体内，通过使用高脂肪饮食和低剂量链脲佐菌素诱导2型糖尿病大鼠模型。通过颈静脉注射携带PHB cDNA的慢病毒来实现模型大鼠中PHB蛋白的过表达。通过代谢测试、超声心动图和组织病理学评估 2 型 DCM 的特征。 DCM 大鼠表现出严重的胰岛素抵抗、左心室功能障碍、纤维化和细胞凋亡。 PHB 过度表达可改善该疾病。体外使用心脏成纤维细胞 (CF) 和 H9c2 心肌细胞研究 PHB 功能改变的机制。在用 HG 处理的 CF 中，PHB 过度表达降低了胶原蛋白的表达、基质金属蛋白酶活性和增殖。在 H9c2 心肌细胞中，PHB 过表达抑制 HG 诱导的细胞凋亡。此外，在 DCM 中，细胞外信号调节激酶 (ERK) 1/2 磷酸化的增加显着降低，Akt 磷酸化的抑制得到恢复。因此，PHB可能成为人类DCM的新治疗靶点。
Prohibitin (PHB) is a highly conserved protein implicated in various cellular functions including proliferation, apoptosis, tumor suppression, transcription, and mitochondrial protein folding. However, its function in diabetic cardiomyopathy (DCM) is still unclear. In vivo, type 2 diabetic rat model was induced by using a high-fat diet and low-dose streptozotocin. Overexpression of the PHB protein in the model rats was achieved by injecting lentivirus carrying PHB cDNA via the jugular vein. Characteristics of type 2 DCM were evaluated by metabolic tests, echocardiography and histopathology. Rats with DCM showed severe insulin resistance, left ventricular dysfunction, fibrosis and apoptosis. PHB overexpression ameliorated the disease. Cardiofibroblasts (CFs) and H9c2 cardiomyoblasts were used in vitro to investigate the mechanism of PHB in altered function. In CFs treated with HG, PHB overexpression decreased expression of collagen, matrix metalloproteinase activity, and proliferation. In H9c2 cardiomyoblasts, PHB overexpression inhibited apoptosis induced by HG. Furthermore, the increased phosphorylation of extracellular signal–regulated kinase (ERK) 1/2 was significantly decreased and the inhibited phosphorylation of Akt was restored in DCM. Therefore, PHB may be a new therapeutic target for human DCM.