title: FAT10 protects cardiac myocytes against apoptosis.
abstract: FAT10 is a new member of the ubiquitin-like protein family with yet-to-be defined biological functions in the heart. Our objective was to determine the role of FAT10 in the heart. FAT10 is expressed in the normal human and murine hearts, as detected by qPCR and Western blotting. Expression of FAT10 is increased in the heart at the border zone of myocardial infarction and in cultured neonatal rat cardiac myocytes (NRCM) subjected to hypoxia/reoxygenation (H/R) stress. Lentiviral-mediated overexpression of FAT10 in NRCM reduced p53 (TP53) and its target miR-34a levels, while BCL2 level, a target of miR-34a, was increased and BAX level, a pro-apoptotic protein, was reduced. These changes were associated with reduced apoptosis, detected by FACS analysis of annexin-V expression and TUNEL assay, in response to H/R injury. Knock down of FAT10 by shRNA targeting had the opposite effects. Likewise, lentiviral mediated expression of miR-34a was associated with reduced BCL2 and increased BAX levels in NRCM and also reversed changes in BCL-2 and BAX levels observed upon over-expression of FAT10. Treatment of NRCM with proteasome inhibitor MG132 increased p53 and miR-34a levels and reduced BLC2/BAX ratio. These changes were not reversed upon over-expression of FAT10. Thus, FAT10 is upregulated in the heart and NRCM in response to H/R stress, which protects cardiac myocytes against apoptosis. The anti-apoptotic effects of FAT10 are associated with suppression of p53, probably through fatylation and proteasomal degradation, reduced miR-34a expression, and a shift in the BCL2/BAX proteins against apoptosis. Thus, FAT10 is a cardioprotective protein.
authors: Cardiovascular Department, the Second Affiliated Hospital of Nanchang University, Nanchang 330006, China; The Key Laboratory of Molecular Medicine, the Second Affiliated Hospital of Nanchang University, Nanchang 330006, China.
authors: Xiaogang
authors: X
authors: Peng
authors: Jianghua
authors: J
authors: Shao
authors: Yang
authors: Y
authors: Shen
authors: Yunguo
authors: Y
authors: Zhou
authors: Qing
authors: Q
authors: Cao
authors: Jinzhu
authors: J
authors: Hu
authors: Wenfeng
authors: W
authors: He
authors: Xin
authors: X
authors: Yu
authors: Xiuxia
authors: X
authors: Liu
authors: Ali J
authors: AJ
authors: Marian
authors: Kui
authors: K
authors: Hong
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics / Q000502:physiology; D002478:Cells, Cultured; D006801:Humans; D008297:Male; D051379:Mice; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism; D017202:Myocardial Ischemia / Q000378:metabolism / Q000473:pathology; D009206:Myocardium / Q000378:metabolism; D032383:Myocytes, Cardiac / Q000166:cytology / Q000378:metabolism* / Q000473:pathology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism; D014452:Ubiquitins / Q000235:genetics / Q000378:metabolism*; D051028:bcl-2-Associated X Protein / Q000235:genetics / Q000378:metabolism
chemical_list: C512253:FAT10 protein, mouse; C560944:MIRN34 microRNA, rat; D035683:MicroRNAs; D019253:Proto-Oncogene Proteins c-bcl-2; D016159:Tumor Suppressor Protein p53; C109184:UBD protein, human; C569926:UbD protein, rat; D014452:Ubiquitins; D051028:bcl-2-Associated X Protein