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Enhanced Calreticulin Expression Promotes Calcium-dependent Apoptosis in Postnatal Cardiomyocytes  

Lim, Soyeon (Cardiovascular Research Institute, Cardiology Division, Department of Internal Medicine, Brain Korea 21 Project for Medical Science, Yonsei University College of Medicine)
Chang, Woochul (Cardiovascular Research Institute, Cardiology Division, Department of Internal Medicine, Brain Korea 21 Project for Medical Science, Yonsei University College of Medicine)
Lee, Byoung Kwon (Department of Internal Medicine, Sanggyepaik Hospital, Inje University)
Song, Heesang (Department of Pediatrics, Washington University in St. Louis School of Medicine)
Hong, Ja Hyun (Cardiovascular Research Institute, Cardiology Division, Department of Internal Medicine, Brain Korea 21 Project for Medical Science, Yonsei University College of Medicine)
Lee, Sunju (Cardiovascular Research Institute, Cardiology Division, Department of Internal Medicine, Brain Korea 21 Project for Medical Science, Yonsei University College of Medicine)
Song, Byeong-Wook (Cardiovascular Research Institute, Cardiology Division, Department of Internal Medicine, Brain Korea 21 Project for Medical Science, Yonsei University College of Medicine)
Kim, Hye-Jung (Cardiovascular Research Institute, Cardiology Division, Department of Internal Medicine, Brain Korea 21 Project for Medical Science, Yonsei University College of Medicine)
Cha, Min-Ji (Cardiovascular Research Institute, Cardiology Division, Department of Internal Medicine, Brain Korea 21 Project for Medical Science, Yonsei University College of Medicine)
Jang, Yangsoo (Cardiovascular Research Institute, Cardiology Division, Department of Internal Medicine, Brain Korea 21 Project for Medical Science, Yonsei University College of Medicine)
Chung, Namsik (Cardiovascular Research Institute, Cardiology Division, Department of Internal Medicine, Brain Korea 21 Project for Medical Science, Yonsei University College of Medicine)
Choi, Soon-Yong (Department of Biotechnology, College of Life Science and Nano Technology, Hannam University)
Hwang, Ki-Chul (Cardiovascular Research Institute, Cardiology Division, Department of Internal Medicine, Brain Korea 21 Project for Medical Science, Yonsei University College of Medicine)
Publication Information
Molecules and Cells / v.25, no.3, 2008 , pp. 390-396 More about this Journal
Abstract
Calreticulin (CRT) is one of the major $Ca^{2+}$ 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 $Ca^{2+}$-dependent signal cascades were investigated using CRT-overexpressing cardiomyocytes. In particular, we asked whether calreticulin plays a critical role in the activation of $Ca^{2+}$-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.
Keywords
Apoptosis; Calcium Overload; Calreticulin; Cardiomyocytes;
Citations & Related Records
Times Cited By KSCI : 1  (Citation Analysis)
Times Cited By Web Of Science : 5  (Related Records In Web of Science)
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