| Abstrakt: |
It is known that the concentrations of long-chain fatty acids (LCFA) and their carnitine derivatives (LCAC) in obesity and diabetes greatly increase, and under conditions of ischemia-reperfusion can exceed tens of μM in the focus of cell damage. The most toxic are LCAC, activated derivatives of LCFA. In this work, we investigated the effect of D, L-acylcarnitines with different carbon chain lengths on the induction of mitochondrial cyclosporin A (CsA)-dependent pore (mPTP). In experiments on isolated rat liver mitochondria, we tested hexanoylcarnitine (HC, C6:0), lauroylcarnitine (LC, C12:0), myristoylcarnitine (MC, C14:0), and palmitoylcarnitine (PC, C16:0); respiration rate of mitochondria, mitochondrial potential (ΔΨ) and swelling of mitochondria during the oxidation of glutamate and pyruvate were recorded in the presence of these acylcarnitines at various concentrations. It was shown that all the studied acylcarnitines cause inhibition of mitochondrial respiration, activated by the ADP-hexokinase system, and also induce mitochondrial swelling. The magnitudes of the observed effects are inversely proportional to the carbon chain length of the acylcarnitines. The critical concentrations of PC, MS, LC, and HC, at which a decrease in ΔΨ occurs, are 100, 110, 500 μM, and 3 mM, respectively. Mitochondrial swelling is induced at threshold concentrations of PC, MC, and LC of 10, 25, and 200 μM, respectively. CsA, EGTA, and ADP increase the threshold concentrations of PC and MS required for the induction of mPTP and are not effective at higher concentrations of acylcarnitines. Thus, among the carnitine derivatives of saturated fatty acids with a carbon chain length of 6 to 16, PC and MC are the most toxic agents capable of inducing mPTP induction. [ABSTRACT FROM AUTHOR] |
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