Destabilization of the cytosolic calcium level and the death of cardiomyocytes in the presence of derivatives of long-chain fatty acids

A. V. Berezhnov, E. I. Fedotova, M. N. Nenov, Yu M. Kokoz, V. P. Zinchenko, V. V. Dynnik

Research output: Contribution to journalArticle

Abstract

By means of fluorescent microscopy, long-chain fatty acid derivatives, myristoylcarnitine and palmitoylcarnitine, were shown to exert the most toxic effect on rat ventricular cardiomyocytes. The addition of 20-50 μM acylcarnitines increased calcium concentration in cytoplasm ([Ca 2+]i) and caused cell death after a lag-period of 4-8 min. This effect was independent of extracellular calcium level and Ca2+ inhibitors of L-type channels. Free myristic and palmitic acids at concentrations of 300-500 μM had little effect on [Ca2+] i within 30 min. We suggest that the toxic effect is due to the activation of calcium channels of sarcoplasmic reticulum by acylcarnitines and/or arising acyl-CoA. Mitochondria play a role of calcium-buffer system under these conditions. The calcium capacity of the buffer determines the duration of the lag-period. Phosphate increases the calcium capacity of mitochondria and the lag-period. In the presence of rotenone and oligomycin, the elevation of [Ca2+]i after the addition of acylcarnitines occurs without the lag-period. The exhaustion of the mitochondrial calcium-buffer capacity or significant depolarization of mitochondria leads to a rapid release of calcium from mitochondria and cell death. Thus, the activation of reticular calcium channels is the main reason of the toxicity of myristoylcarnitine and palmitoylcarnitine.

Original languageEnglish (US)
Pages (from-to)564-570
Number of pages7
JournalBiophysics
Volume53
Issue number6
DOIs
StatePublished - Dec 2008
Externally publishedYes

Fingerprint

Cardiac Myocytes
Fatty Acids
Calcium
Mitochondria
Palmitoylcarnitine
Buffers
Poisons
Calcium Channels
Myristic Acids
Cell Death
Palmitic Acids
Oligomycins
Rotenone
Acyl Coenzyme A
Sarcoplasmic Reticulum
Microscopy
Cytoplasm
acylcarnitine

Keywords

  • [Ca]
  • Cardiomyocytes
  • Fatty acids
  • Mitochondria
  • Mitochondrial [Ca]-capacity
  • Myristoylcarnitine
  • Palmitoylcarnitine
  • Ryanodine receptor

ASJC Scopus subject areas

  • Biophysics

Cite this

Berezhnov, A. V., Fedotova, E. I., Nenov, M. N., Kokoz, Y. M., Zinchenko, V. P., & Dynnik, V. V. (2008). Destabilization of the cytosolic calcium level and the death of cardiomyocytes in the presence of derivatives of long-chain fatty acids. Biophysics, 53(6), 564-570. https://doi.org/10.1134/S0006350908060183

Destabilization of the cytosolic calcium level and the death of cardiomyocytes in the presence of derivatives of long-chain fatty acids. / Berezhnov, A. V.; Fedotova, E. I.; Nenov, M. N.; Kokoz, Yu M.; Zinchenko, V. P.; Dynnik, V. V.

In: Biophysics, Vol. 53, No. 6, 12.2008, p. 564-570.

Research output: Contribution to journalArticle

Berezhnov, A. V. ; Fedotova, E. I. ; Nenov, M. N. ; Kokoz, Yu M. ; Zinchenko, V. P. ; Dynnik, V. V. / Destabilization of the cytosolic calcium level and the death of cardiomyocytes in the presence of derivatives of long-chain fatty acids. In: Biophysics. 2008 ; Vol. 53, No. 6. pp. 564-570.
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