title: Apoptosis Inducing Factor Is Involved in Stretch-Induced Apoptosis of Myoblast via a Caspase-9 Independent Pathway.
abstract: The apoptosis of myoblast in response to excessive cyclic stretch is crucial in adaptive construction of skeletal muscles in orthopedic functional therapy. Mitochondria signaling pathway is the central links in the execution of the intrinsic apoptotic cascade, but its molecular mechanism in stretch-induced apoptosis in myoblasts remains incompletely understood. The aim of this study was to investigate the mechanobiological roles of caspase-9 and Apoptosis Inducing Factor (AIF), two important components in mitochondrial pathway, in stretch-induced apoptosis of myoblast. Hoechst 33258 was used to observe apoptotic cells morphologically and flow cytometry to analyze apoptosis rate of myoblasts. Protein and mRNA of caspase-9 and AIF were detected by Western blotting and RT-PCR. Furthermore, caspase-9 specific inhibitor z-LEHD-fmk was applied to clear the mechanism of caspase-9 pathway in stretch-induced apoptosis. We found that apoptotic rate induced by cyclic stretch increased in a time-dependent manner, and the same tendency of mRNA and protein of caspase-9 and AIF. Caspase-9 inhibition reduced stretch-induced apoptosis, but had no effect on expression of AIF. We concluded that caspase-9 and AIF played an important role in stretch-induced apoptosis in myoblast, and AIF was involved in the process in a caspase-9 independent way. J. Cell. Biochem. 118: 829-838, 2017. © 2016 Wiley Periodicals, Inc.
authors.affiliation: Department of Orthodontics, The Affiliated Qingdao Municipal Hospital, Qingdao University, Qingdao, Shandong Province, 266011, People's Republic of China.
authors.forename: Fang
authors.initials: F
authors.lastname: Wang
authors.affiliation: Department of Orthodontics, Jinan Stomatological Hospital, Jinan, Shandong Province, 250001, People's Republic of China.
authors.forename: Zhu-Liang
authors.initials: ZL
authors.lastname: Wei
authors.affiliation: Department of Orthodontics, Weihai Stomatological Hospital, Weihai, Shandong Province, 264200, People's Republic of China.
authors.forename: Xian-Rui
authors.initials: XR
authors.lastname: Sun
authors.affiliation: Department of Orthodontics, The Affiliated Qingdao Municipal Hospital, Qingdao University, Qingdao, Shandong Province, 266011, People's Republic of China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: Department of Orthodontics, The Affiliated Qingdao Municipal Hospital, Qingdao University, Qingdao, Shandong Province, 266011, People's Republic of China.
authors.forename: Cai-Xia
authors.initials: CX
authors.lastname: Zhang
authors.affiliation: Department of Orthodontics, The Affiliated Qingdao Municipal Hospital, Qingdao University, Qingdao, Shandong Province, 266011, People's Republic of China.
authors.forename: Wen-Xin
authors.initials: WX
authors.lastname: Jiang
authors.affiliation: Department of Orthodontics, The Affiliated Qingdao Municipal Hospital, Qingdao University, Qingdao, Shandong Province, 266011, People's Republic of China.
authors.forename: Xiao
authors.initials: X
authors.lastname: Yan
authors.affiliation: Department of Orthodontics, The Affiliated Qingdao Municipal Hospital, Qingdao University, Qingdao, Shandong Province, 266011, People's Republic of China.
authors.forename: Jia-Ning
authors.initials: JN
authors.lastname: Liu
authors.affiliation: Department of Orthodontics, The Affiliated Qingdao Municipal Hospital, Qingdao University, Qingdao, Shandong Province, 266011, People's Republic of China.
authors.forename: Xiao
authors.initials: X
authors.lastname: Yuan
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D051033:Apoptosis Inducing Factor / Q000235:genetics / Q000378:metabolism*; D053453:Caspase 9 / Q000235:genetics / Q000378:metabolism*; D061945:Caspase Inhibitors / Q000494:pharmacology; D002460:Cell Line; D008931:Mitochondria, Muscle / Q000378:metabolism; D032446:Myoblasts / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D009842:Oligopeptides / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D015398:Signal Transduction; D013314:Stress, Mechanical
chemical_list: C494831:Aifm1 protein, rat; D051033:Apoptosis Inducing Factor; D061945:Caspase Inhibitors; D009842:Oligopeptides; D012333:RNA, Messenger; C403754:benzyloxycarbonyl-leucyl-glutamyl-histidyl-aspartic acid fluoromethyl ketone; C506435:Casp9 protein, rat; D053453:Caspase 9
keywords: AIF; APOPTOSIS; CASPASE-9; CYCLIC STRETCH; MYOBLAST