title: Nogo-C regulates cardiomyocyte apoptosis during mouse myocardial infarction.
abstract: Myocardial infarction is caused by insufficient coronary blood supply, which leads to myocardial damage and eventually the heart failure. Molecular mechanisms associated with the loss of cardiomyocytes during myocardial infarction (MI) and ischemia-related cardiac diseases are not yet fully understood. Nogo-C is an endoplasmic reticulum protein ubiquitously expressed in tissues including in the heart, however, the cardiac function of Nogo-C is still unknown. In the present study, we found that Nogo-C was upregulated in mouse hearts after MI, and hypoxic treatments also increased Nogo-C protein level in cardiomyocytes. Adenovirus mediated overexpression of Nogo-C led to cardiomyocyte apoptosis, whereas knockdown of Nogo-c by shRNA protected cardiomyocytes from hypoxia-induced cell apoptosis. Importantly, Nogo-C knockout mice displayed improved cardiac function, smaller infarct area, and less apoptotic cells after MI. Moreover, we found that miR-182 negatively regulated Nogo-C expression and was downregulated during MI, expressing miR-182 in cardiomyocytes protected hypoxia- and Nogo-C-mediated cell apoptosis. Our results indicate that increased cardiac Nogo-C expression is both sufficient and necessary for ischemia-induced cardiomyocyte apoptosis and cardiac dysfunction, suggesting that deregulation of Nogo-C by miRNA may be a potential therapeutic target for ischemia-related heart diseases.
authors.affiliation: Department of Physiology and Pathophysiology, Health Science Center, Peking University, Beijing 100191, China.
authors.forename: Shi
authors.initials: S
authors.lastname: Jia
authors.affiliation: Department of Physiology and Pathophysiology, Health Science Center, Peking University, Beijing 100191, China.
authors.forename: Xue
authors.initials: X
authors.lastname: Qiao
authors.affiliation: Department of Physiology and Pathophysiology, Health Science Center, Peking University, Beijing 100191, China.
authors.forename: Jingjing
authors.initials: J
authors.lastname: Ye
authors.affiliation: Department of Physiology and Pathophysiology, Health Science Center, Peking University, Beijing 100191, China.
authors.forename: Xuan
authors.initials: X
authors.lastname: Fang
authors.affiliation: Department of Physiology and Pathophysiology, Health Science Center, Peking University, Beijing 100191, China.
authors.forename: Chunling
authors.initials: C
authors.lastname: Xu
authors.affiliation: Department of Physiology and Pathophysiology, Health Science Center, Peking University, Beijing 100191, China.
authors.forename: Yangpo
authors.initials: Y
authors.lastname: Cao
authors.affiliation: Department of Physiology and Pathophysiology, Health Science Center, Peking University, Beijing 100191, China.
authors.forename: Ming
authors.initials: M
authors.lastname: Zheng
mesh_terms: D000818:Animals; D017209:Apoptosis; D001483:Base Sequence; D015687:Cell Hypoxia; D008297:Male; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism; D009203:Myocardial Infarction / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000473:pathology* / Q000503:physiopathology; D032383:Myocytes, Cardiac / Q000378:metabolism* / Q000473:pathology*; D000070798:Nogo Proteins / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation
chemical_list: D035683:MicroRNAs; C540524:Mirn182 microRNA, mouse; D000070798:Nogo Proteins