title: Enhanced calreticulin expression promotes calcium-dependent apoptosis in postnatal cardiomyocytes.
abstract: Calreticulin (CRT) is one of the major Ca2+ binding chaperone proteins of the endoplasmic reticulum (ER) and an unusual luminal ER protein. Postnatally elevated expression of CRT leads to impaired development of the cardiac conductive system and may be responsible for the pathology of complete heart block. In this study, the molecular mechanisms that affect Ca2+-dependent signal cascades were investigated using CRT-overexpressing cardiomyocytes. In particular, we asked whether calreticulin plays a critical role in the activation of Ca2+-dependent apoptosis. In the cells overexpressing CRT, the intracellular calcium concentration was significantly increased and the activity of PKC and level of SECAR2a mRNA were reduced. Phosphorylation of Akt and ERKs decreased compared to control. In addition the activity of the anti-apoptotic factor, Bcl-2, was decreased and the activities of pro-apoptotic factor, Bax, p53 and caspase 8 were increased, leading to a dramatic augmentation of caspase 3 activity. Our results suggest that enhanced CRT expression in mature cardiomyocytes disrupts intracellular calcium regulation, leading to calcium-dependent apoptosis.
authors.affiliation: Cardiovascular Research Institute, Cardiology Division, Department of Internal Medicine, Brain Korea 21 Project for Medical Science, Yonsei University College of Medicine, Seoul 120-752, Korea.
authors.forename: Soyeon
authors.initials: S
authors.lastname: Lim
authors.forename: Woochul
authors.initials: W
authors.lastname: Chang
authors.forename: Byoung Kwon
authors.initials: BK
authors.lastname: Lee
authors.forename: Heesang
authors.initials: H
authors.lastname: Song
authors.forename: Ja Hyun
authors.initials: JH
authors.lastname: Hong
authors.forename: Sunju
authors.initials: S
authors.lastname: Lee
authors.forename: Byeong-Wook
authors.initials: BW
authors.lastname: Song
authors.forename: Hye-Jung
authors.initials: HJ
authors.lastname: Kim
authors.forename: Min-Ji
authors.initials: MJ
authors.lastname: Cha
authors.forename: Yangsoo
authors.initials: Y
authors.lastname: Jang
authors.forename: Namsik
authors.initials: N
authors.lastname: Chung
authors.forename: Soon-Yong
authors.initials: SY
authors.lastname: Choi
authors.forename: Ki-Chul
authors.initials: KC
authors.lastname: Hwang
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis; D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling; D037282:Calreticulin / Q000378:metabolism*; D002470:Cell Survival; D002478:Cells, Cultured; D006321:Heart / Q000196:embryology; D032383:Myocytes, Cardiac / Q000166:cytology / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D037282:Calreticulin; D002118:Calcium