Prohibitin overexpression improves myocardial function in diabetic cardiomyopathy

// Wen-qian Dong 1 , Min Chao 5 , Qing-hua Lu 2 , Wei-li Chai 4 , Wei Zhang 1 , Xue-ying Chen 1 , Er-shun Liang 1 , Ling-bo Wang 1 , Hong-liang Tian 1 , Yu-guo Chen 1,3 and Ming-xiang Zhang 1 1 The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Public Health, Qilu Hospital, Shandong University, Jinan, China 2 Department of Cardiology, The Second Hospital of Shandong University, Jinan, China 3 Department of Emergency, Qilu Hospital, Shandong University, Jinan, China 4 Department of Cardiology, The Third Hospital of Jinan, Shandong, China 5 Department of Anorectal Surgery, Affiliated Hospital of Jining Medical College, Jining, Shandong, China Correspondence to: Ming-xiang Zhang, email: // Yu-guo Chen, email: // Keywords : prohibitin, myocardial fibrosis, apoptosis, diabetic cardiomyopathy, Pathology Section Received : August 01, 2015 Accepted : November 16, 2015 Published : November 25, 2015 Abstract 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.