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 Son, Hye Jung Kim, Min Ji Cha, Yangsoo Jang, Namsik Chung, Soon Yong Choi, Ki Chul Hwang

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23 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)390-396
Number of pages7
JournalMolecules and cells
Volume25
Issue number3
Publication statusPublished - 2008 May 31

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Cell Biology

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    Lim, S., Chang, W., Lee, B. K., Song, H., Hong, J. H., Lee, S., Son, B. W., Kim, H. J., Cha, M. J., Jang, Y., Chung, N., Choi, S. Y., & Hwang, K. C. (2008). Enhanced calreticulin expression promotes calcium-dependent apoptosis in postnatal cardiomyocytes. Molecules and cells, 25(3), 390-396.