title: Role of Ca2+ signaling in initiation of stretch-induced apoptosis in neonatal heart cells.
abstract: Abnormal mechanical load, as seen in hypertension, is found to induce heart cell apoptosis, yet the signaling link between cell stretch and apoptotic pathways is not known. Using an in vitro stretch model mimicking diastolic pressure stress, here we show that Ca(2+) signaling participates essentially in the early stage of stretch-induced apoptosis. In neonatal rat cardiomyocytes, the moderate 20% stretch resulted in tonic elevation of intracellular free Ca(2+) ([Ca(2+)](i)). Buffering [Ca(2+)](i) by EGTA-AM, suppressing ryanodine-sensitive Ca(2+) release, and blocking L-type Ca(2+) channels all prevented the stretch-induced apoptosis as assessed by phosphatidylserine exposure and nuclear fragmentation. Notably, Ca(2+) suppression also prevented known stretch-activated apoptotic events, including caspase-3/-9 activation, mitochondrial membrane potential corruption, and reactive oxygen species production, suggesting that Ca(2+) signaling is the upstream of these events. Since [Ca(2+)](i) did not change without activating mechanosensitive Ca(2+) entry, we conclude that stretch-induced Ca(2+) entry, via the Ca(2+)-induced Ca(2+) release mechanism, plays an important role in initiating apoptotic signaling during mechanical stress.
authors.affiliation: Cardiovascular Institute, Peking Union Medical College, Beijing 100037, China.
authors.forename: Xu Dong
authors.initials: XD
authors.lastname: Liao
authors.forename: Ai Hui
authors.initials: AH
authors.lastname: Tang
authors.forename: Quan
authors.initials: Q
authors.lastname: Chen
authors.forename: Hai Jing
authors.initials: HJ
authors.lastname: Jin
authors.forename: Cai Hong
authors.initials: CH
authors.lastname: Wu
authors.forename: Lan-Ying
authors.initials: LY
authors.lastname: Chen
authors.forename: Shi Qiang
authors.initials: SQ
authors.lastname: Wang
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis; D002118:Calcium / Q000378:metabolism; D020013:Calcium Signaling; D006321:Heart / Q000254:growth & development; D017136:Ion Transport; D007700:Kinetics; D032383:Myocytes, Cardiac / Q000166:cytology / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D013314:Stress, Mechanical
chemical_list: D002118:Calcium