Altered Ca 2+ homeostasis and impaired mitochondrial function in cardiomyopathy

T. H. Kuo, L. Zhu, K. Golden, J. D. Marsh, Syamal Bhattacharya, B. F. Liu

Research output: Contribution to journalArticle

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Abstract

Altered Ca 2+ homeostasis and myocyte death is a major characteristic of the hereditary cardiomyopathy in the dystrophic hamster. Despite numerous studies, the mechanisms that link calcium dysregulation and cell death in this animal model remain unclear. We have shown previously that the maintenance of mitochondrial Ca 2+ homeostasis is essential for cell survival, and that loss of mitochondrial Ca 2+ is closely correlated with cell death in cultured cells. Here, we have further investigated the role of mitochondrial Na + -Ca 2+ exchange (NCE) in the development of cardiomyopathy in the dystrophic hamster. We found that the myocyte death was associated with elevated NCE activity together with a reduced level of matrix Ca 2+ , and impaired mitochondrial energetics. The upregulation of NCE activity in myopathic heart was also accompanied by enhanced expression of the sarcolemmal Na + -Ca 2+ exchange (NCX) without alterations in the L-type Ca 2+ channel expression. Treatment of dystrophic hamsters with diltiazem (a potent inhibitor of NCE and Ca 2+ channels) prevented the occurrence of cell death and restored the normal expression of NCX. Our findings implicate the dysregulation of both sarcolemmal and mitochondrial Na + -Ca 2+ exchange in cell death in the myopathic heart.

Original languageEnglish (US)
Pages (from-to)119-127
Number of pages9
JournalMolecular and Cellular Biochemistry
Volume238
Issue number1-2
DOIs
StatePublished - Sep 1 2002

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Cell death
Cardiomyopathies
Homeostasis
Cell Death
Cricetinae
Muscle Cells
Cells
Diltiazem
Cultured Cells
Cell Survival
Animals
Up-Regulation
Animal Models
Maintenance
Calcium

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Clinical Biochemistry
  • Cell Biology

Cite this

Altered Ca 2+ homeostasis and impaired mitochondrial function in cardiomyopathy . / Kuo, T. H.; Zhu, L.; Golden, K.; Marsh, J. D.; Bhattacharya, Syamal; Liu, B. F.

In: Molecular and Cellular Biochemistry, Vol. 238, No. 1-2, 01.09.2002, p. 119-127.

Research output: Contribution to journalArticle

Kuo, T. H. ; Zhu, L. ; Golden, K. ; Marsh, J. D. ; Bhattacharya, Syamal ; Liu, B. F. / Altered Ca 2+ homeostasis and impaired mitochondrial function in cardiomyopathy In: Molecular and Cellular Biochemistry. 2002 ; Vol. 238, No. 1-2. pp. 119-127.
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