Destabilization of the cytosolic calcium level and cardiomyocyte death in the presence of long-chain fatty acid derivatives

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

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

It has been shown using the fluorescent microscopy technique that long-chain fatty acid derivatives, myristoylcarnitine and palmitoylcarnitine, exert the most toxic effect on rat ventricular cardiomyoctes. The addition of 20-50 microM acylcarnitines increases calcium concentration in cytoplasm ([Ca2+]i) and causes cell death after the 4-8 min lag-period. This effect is independent on extracellular calcium and L-type calcium channel inhibitors. Free acids (myristic and palmitic acids) at a concentration of 300-500 microM have a little effect on [Ca2+]i within 30 min. We suggest that the toxic effect is due to the activation of sarcoplasmic reticulum calcium channels by acylcarnitines and resulting acyl-CoA. Mitochondria play a role of calcium-buffer system in these conditions. The calcium capacity of this buffer determines the lag-period. Phosphate increases the calcium capacity of mitochondrial 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 mitochondrial 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)1025-1032
Number of pages8
JournalBiofizika
Volume53
Issue number6
StatePublished - Nov 2008
Externally publishedYes

Fingerprint

Cardiac Myocytes
Fatty Acids
Calcium
Palmitoylcarnitine
Buffers
Poisons
Calcium Channels
Myristic Acids
Mitochondria
Cell Death
Palmitic Acids
Oligomycins
Rotenone
L-Type Calcium Channels
Acyl Coenzyme A
Sarcoplasmic Reticulum
Cause of Death
Microscopy
Cytoplasm
Acids

ASJC Scopus subject areas

  • Biophysics

Cite this

Berezhnov, A. V., Fedotova, E. I., Nenov, M. N., Kokoz, I. M., Zinchenko, V. P., & Dynnik, V. V. (2008). Destabilization of the cytosolic calcium level and cardiomyocyte death in the presence of long-chain fatty acid derivatives. Biofizika, 53(6), 1025-1032.

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

In: Biofizika, Vol. 53, No. 6, 11.2008, p. 1025-1032.

Research output: Contribution to journalArticle

Berezhnov, AV, Fedotova, EI, Nenov, MN, Kokoz, IM, Zinchenko, VP & Dynnik, VV 2008, 'Destabilization of the cytosolic calcium level and cardiomyocyte death in the presence of long-chain fatty acid derivatives', Biofizika, vol. 53, no. 6, pp. 1025-1032.
Berezhnov AV, Fedotova EI, Nenov MN, Kokoz IM, Zinchenko VP, Dynnik VV. Destabilization of the cytosolic calcium level and cardiomyocyte death in the presence of long-chain fatty acid derivatives. Biofizika. 2008 Nov;53(6):1025-1032.
Berezhnov, A. V. ; Fedotova, E. I. ; Nenov, M. N. ; Kokoz, I. M. ; Zinchenko, V. P. ; Dynnik, V. V. / Destabilization of the cytosolic calcium level and cardiomyocyte death in the presence of long-chain fatty acid derivatives. In: Biofizika. 2008 ; Vol. 53, No. 6. pp. 1025-1032.
@article{4db2487f296e4bdeb97ae9a3da38b613,
title = "Destabilization of the cytosolic calcium level and cardiomyocyte death in the presence of long-chain fatty acid derivatives",
abstract = "It has been shown using the fluorescent microscopy technique that long-chain fatty acid derivatives, myristoylcarnitine and palmitoylcarnitine, exert the most toxic effect on rat ventricular cardiomyoctes. The addition of 20-50 microM acylcarnitines increases calcium concentration in cytoplasm ([Ca2+]i) and causes cell death after the 4-8 min lag-period. This effect is independent on extracellular calcium and L-type calcium channel inhibitors. Free acids (myristic and palmitic acids) at a concentration of 300-500 microM have a little effect on [Ca2+]i within 30 min. We suggest that the toxic effect is due to the activation of sarcoplasmic reticulum calcium channels by acylcarnitines and resulting acyl-CoA. Mitochondria play a role of calcium-buffer system in these conditions. The calcium capacity of this buffer determines the lag-period. Phosphate increases the calcium capacity of mitochondrial 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 mitochondrial 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.",
author = "Berezhnov, {A. V.} and Fedotova, {E. I.} and Nenov, {M. N.} and Kokoz, {I. M.} and Zinchenko, {V. P.} and Dynnik, {V. V.}",
year = "2008",
month = "11",
language = "English (US)",
volume = "53",
pages = "1025--1032",
journal = "Biofizika",
issn = "0006-3029",
publisher = "Izdatel'stvo Nauka",
number = "6",

}

TY - JOUR

T1 - Destabilization of the cytosolic calcium level and cardiomyocyte death in the presence of long-chain fatty acid derivatives

AU - Berezhnov, A. V.

AU - Fedotova, E. I.

AU - Nenov, M. N.

AU - Kokoz, I. M.

AU - Zinchenko, V. P.

AU - Dynnik, V. V.

PY - 2008/11

Y1 - 2008/11

N2 - It has been shown using the fluorescent microscopy technique that long-chain fatty acid derivatives, myristoylcarnitine and palmitoylcarnitine, exert the most toxic effect on rat ventricular cardiomyoctes. The addition of 20-50 microM acylcarnitines increases calcium concentration in cytoplasm ([Ca2+]i) and causes cell death after the 4-8 min lag-period. This effect is independent on extracellular calcium and L-type calcium channel inhibitors. Free acids (myristic and palmitic acids) at a concentration of 300-500 microM have a little effect on [Ca2+]i within 30 min. We suggest that the toxic effect is due to the activation of sarcoplasmic reticulum calcium channels by acylcarnitines and resulting acyl-CoA. Mitochondria play a role of calcium-buffer system in these conditions. The calcium capacity of this buffer determines the lag-period. Phosphate increases the calcium capacity of mitochondrial 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 mitochondrial 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.

AB - It has been shown using the fluorescent microscopy technique that long-chain fatty acid derivatives, myristoylcarnitine and palmitoylcarnitine, exert the most toxic effect on rat ventricular cardiomyoctes. The addition of 20-50 microM acylcarnitines increases calcium concentration in cytoplasm ([Ca2+]i) and causes cell death after the 4-8 min lag-period. This effect is independent on extracellular calcium and L-type calcium channel inhibitors. Free acids (myristic and palmitic acids) at a concentration of 300-500 microM have a little effect on [Ca2+]i within 30 min. We suggest that the toxic effect is due to the activation of sarcoplasmic reticulum calcium channels by acylcarnitines and resulting acyl-CoA. Mitochondria play a role of calcium-buffer system in these conditions. The calcium capacity of this buffer determines the lag-period. Phosphate increases the calcium capacity of mitochondrial 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 mitochondrial 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.

UR - http://www.scopus.com/inward/record.url?scp=61549140375&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=61549140375&partnerID=8YFLogxK

M3 - Article

C2 - 19137688

AN - SCOPUS:61549140375

VL - 53

SP - 1025

EP - 1032

JO - Biofizika

JF - Biofizika

SN - 0006-3029

IS - 6

ER -