title: Caspase-12 is involved in stretch-induced apoptosis mediated endoplasmic reticulum stress.
abstract: It is well recognized that mandibular growth, which is caused by a variety of functional appliances, is considered to be the result of both neuromuscular and skeletal adaptations. Accumulating evidence has demonstrated that apoptosis plays an important role in the adaptation of skeletal muscle function. However, the underlying mechanism of apoptosis that is induced by stretch continues to be incompletely understood. Endoplasmic reticulum stress (ERS), a newly defined signaling pathway, initiates apoptosis. This study seeks to determine if caspase-12 is involved in stretch-induced apoptosis mediated endoplasmic reticulum stress in myoblast and its underlying mechanism. Apoptosis was assessed by Hochest staining, DAPI staining and annexin V binding and PI staining. ER chaperones, such as GRP78, CHOP and caspase-12, were determined by reverse transcription polymerase chain reaction (RT-PCR) and Western blot. Furthermore, caspase-12 inhibitor was used to value the mechanism of the caspase-12 pathway. Apoptosis of myoblast, which is subjected to cyclic stretch, was observed in a time-dependent manner. We found that GRP78 mRNA and protein were significantly increased and CHOP and caspase-12 were activated in myoblast that was exposed to cyclic stretch. Caspase-12 inhibition reduced stretch-induced apoptosis, and caspase-12 activated caspase-3 to induce apoptosis. We concluded that caspase-12 played an important role in stretch-induced apoptosis that is associated by endoplasmic reticulum stress by activating caspase-3.
authors.affiliation: Department of Orthodontics, Qingdao Municipal Hospital, Qingdao, 266011, Shandong, People's Republic of China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: Qingdao Municipal Hospital, Qingdao, 266011, Shandong, People's Republic of China.
authors.forename: Jianing
authors.initials: J
authors.lastname: Liu
authors.affiliation: Qingdao Municipal Hospital, Qingdao, 266011, Shandong, People's Republic of China.
authors.forename: Shulan
authors.initials: S
authors.lastname: Chen
authors.affiliation: Qingdao Municipal Hospital, Qingdao, 266011, Shandong, People's Republic of China.
authors.forename: Jing
authors.initials: J
authors.lastname: Liu
authors.affiliation: People's of Weifang Hospital, Weifang, 261041, Shandong, People's Republic of China.
authors.forename: Lijuan
authors.initials: L
authors.lastname: Liu
authors.affiliation: Department of Orthodontics, Qingdao Municipal Hospital, Qingdao, 266011, Shandong, People's Republic of China.
authors.forename: Guirong
authors.initials: G
authors.lastname: Liu
authors.affiliation: Department of Orthodontics, Qingdao Municipal Hospital, Qingdao, 266011, Shandong, People's Republic of China.
authors.forename: Fang
authors.initials: F
authors.lastname: Wang
authors.affiliation: Department of Orthodontics, Qingdao Municipal Hospital, Qingdao, 266011, Shandong, People's Republic of China.
authors.forename: Wenxin
authors.initials: W
authors.lastname: Jiang
authors.affiliation: Department of Orthodontics, Qingdao Municipal Hospital, Qingdao, 266011, Shandong, People's Republic of China.
authors.forename: Caixia
authors.initials: C
authors.lastname: Zhang
authors.affiliation: Department of Stomatology, People's Hospital in Qingdao Shibei District, Qingdao, 266011, Shandong, People's Republic of China.
authors.forename: Shuangyu
authors.initials: S
authors.lastname: Wang
authors.affiliation: Department of Orthodontics, Qingdao Municipal Hospital, Qingdao, 266011, Shandong, People's Republic of China. yuanxiaoqd@163.com.
authors.forename: Xiao
authors.initials: X
authors.lastname: Yuan
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D053454:Caspase 12 / Q000235:genetics / Q000378:metabolism*; D053148:Caspase 3 / Q000378:metabolism*; D061945:Caspase Inhibitors / Q000494:pharmacology; D002460:Cell Line; D059865:Endoplasmic Reticulum Stress / Q000502:physiology*; D004789:Enzyme Activation; D006360:Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism*; D032446:Myoblasts / Q000378:metabolism*; D051381:Rats; D015398:Signal Transduction / Q000502:physiology; D051742:Transcription Factor CHOP / Q000235:genetics / Q000378:metabolism*; D000091342:Endoplasmic Reticulum Chaperone BiP
chemical_list: D053454:Caspase 12; D053148:Caspase 3; D061945:Caspase Inhibitors; D006360:Heat-Shock Proteins; D051742:Transcription Factor CHOP; C497251:Ddit3 protein, rat; C051684:GRP78 protein, rat; D000091342:Endoplasmic Reticulum Chaperone BiP; C506443:Casp12 protein, rat; C505410:Casp3 protein, rat
keywords: Apoptosis; Caspase-12; Cyclic stretch; Endoplasmic reticulum stress; Myoblast