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Enhanced calreticulin expression promotes calcium-dependent apoptosis in postnatal cardiomyocytes

 Soyeon Lim  ;  Woochul Chang  ;  Byoung Kwon Lee  ;  Heesang Song  ;  Ja Hyun Hong  ;  Sunju Lee  ;  Byeong-Wook Song  ;  Hye-Jung Kim  ;  Min-Ji Cha  ;  Yangsoo Jang  ;  Namsik Chung  ;  Soon-Yong Choi  ;  Ki-Chul Hwang 
 MOLECULES AND CELLS, Vol.25(3) : 390-396, 2008 
Journal Title
Issue Date
Animals ; Animals, Newborn ; Apoptosis* ; Calcium/metabolism* ; Calcium Signaling ; Calreticulin/metabolism* ; Cell Survival ; Cells, Cultured ; Heart/embryology ; Myocytes, Cardiac/cytology ; Myocytes, Cardiac/metabolism* ; Rats ; Rats, Sprague-Dawley
Apoptosis ; Calcium overload ; Calreticulin ; Cardiomyocytes
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.
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1. College of Medicine (의과대학) > Yonsei Biomedical Research Center (연세의생명연구원) > 1. Journal Papers
1. College of Medicine (의과대학) > BioMedical Science Institute (의생명과학부) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Medical Research Center (임상의학연구센터) > 1. Journal Papers
Yonsei Authors
Kim, Hye Jung(김혜정)
Song, Byeong Wook(송병욱)
Lee, Sun Ju(이선주)
Lim, So Yeon(임소연)
Jang, Yang Soo(장양수) ORCID logo https://orcid.org/0000-0002-2169-3112
Chang, Woo Chul(장우철)
Chung, Nam Sik(정남식)
Cha, Min Ji(차민지)
Hwang, Ki Chul(황기철)
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