title: Prohibitin overexpression improves myocardial function in diabetic cardiomyopathy.
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.
authors.affiliation: 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.
authors.forename: Wen-qian
authors.initials: WQ
authors.lastname: Dong
authors.affiliation: Department of Anorectal Surgery, Affiliated Hospital of Jining Medical College, Jining, Shandong, China.
authors.forename: Min
authors.initials: M
authors.lastname: Chao
authors.affiliation: Department of Cardiology, The Second Hospital of Shandong University, Jinan, China.
authors.forename: Qing-hua
authors.initials: QH
authors.lastname: Lu
authors.affiliation: Department of Cardiology, The Third Hospital of Jinan, Shandong, China.
authors.forename: Wei-li
authors.initials: WL
authors.lastname: Chai
authors.affiliation: 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.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.affiliation: 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.
authors.forename: Xue-ying
authors.initials: XY
authors.lastname: Chen
authors.affiliation: 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.
authors.forename: Er-shun
authors.initials: ES
authors.lastname: Liang
authors.affiliation: 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.
authors.forename: Ling-bo
authors.initials: LB
authors.lastname: Wang
authors.affiliation: 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.
authors.forename: Hong-liang
authors.initials: HL
authors.lastname: Tian
authors.affiliation: 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.|Department of Emergency, Qilu Hospital, Shandong University, Jinan, China.
authors.forename: Yu-guo
authors.initials: YG
authors.lastname: Chen
authors.affiliation: 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.
authors.forename: Ming-xiang
authors.initials: MX
authors.lastname: Zhang
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis / Q000235:genetics; D015153:Blotting, Western; D009202:Cardiomyopathies / Q000209:etiology / Q000235:genetics / Q000503:physiopathology*; D002460:Cell Line; D002478:Cells, Cultured; D003921:Diabetes Mellitus, Experimental / Q000209:etiology / Q000235:genetics / Q000503:physiopathology*; D003924:Diabetes Mellitus, Type 2 / Q000209:etiology / Q000235:genetics / Q000503:physiopathology*; D059305:Diet, High-Fat / Q000009:adverse effects; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005355:Fibrosis / Q000235:genetics; D015870:Gene Expression; D006334:Heart Function Tests; D006801:Humans; D007333:Insulin Resistance / Q000235:genetics; D008297:Male; D008856:Microscopy, Fluorescence; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D010766:Phosphorylation; D000091402:Prohibitins; D017207:Rats, Sprague-Dawley; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D018487:Ventricular Dysfunction, Left / Q000235:genetics
chemical_list: C000717328:PHB protein, human; C000717332:Phb protein, rat; D000091402:Prohibitins; D012097:Repressor Proteins; D048049:Extracellular Signal-Regulated MAP Kinases
keywords: Pathology Section; apoptosis; diabetic cardiomyopathy; myocardial fibrosis; prohibitin