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Mol. Cells 2008; 25(3): 390-396

Published online January 1, 1970

© The Korean Society for Molecular and Cellular Biology

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, Nam-Sik Chung, Soon-Yong Choi and Ki-Chul Hwang

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.

Keywords Apoptosis, Calcium overload, Calreticulin, Cardiomyocytes

Article

Research Article

Mol. Cells 2008; 25(3): 390-396

Published online May 31, 2008

Copyright © The Korean Society for Molecular and Cellular Biology.

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, Nam-Sik Chung, Soon-Yong Choi and Ki-Chul Hwang

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.

Keywords: Apoptosis, Calcium overload, Calreticulin, Cardiomyocytes

Mol. Cells
Nov 30, 2023 Vol.46 No.11, pp. 655~725
COVER PICTURE
Kim et al. (pp. 710-724) demonstrated that a pathogen-derived Ralstonia pseudosolanacearum type III effector RipL delays flowering time and enhances susceptibility to bacterial infection in Arabidopsis thaliana. Shown is the RipL-expressing Arabidopsis plant, which displays general dampening of the transcriptional program during pathogen infection, grown in long-day conditions.

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