Efeitos de acido araquidonico na homeostase intracelular de calcio

AUTOR(ES)
DATA DE PUBLICAÇÃO

2001

RESUMO

Calcium ions play essential role in the control of many cellular functions, however the excess may act as a trigger for both programmed (apoptosis) or accidental cell death (necrosis). To evaluate the role of arachidonic acid (AA) in intracellular calcium homeostases, we used two experimental models: isolated rat liver mitochondria and trypanosomatids. We have compared the PTP opening ability of AA with that of carbonyl cyanide m-chlorophenylhydrazone (FCCP) at concentrations that cause similar quantitative dissipation of the membrane potential (? ?) in Ca2+-Ioaded rat liver mitochondria respiring on succinate. The protonophoric effects of AA and FCCP were only slightly modified by carboxyatractyloside and were followed by PTP opening, sensitive to catalase, EGTA, ADP, dithiothreitol, cyclosporin A, rotenone or NAD(P)H-linked substrates. These results indicate that a condition of oxidative stress associated with the oxidized state of PN underlies membrane protein thiol oxidation and PTP opening. We also studied the AA induced-calcium mobilization in Trypanosoma brucei procyclic trypomastigotes, Leishmania donovani promastigotes and Trypanosoma cruzi amastigotes. We verified that Ca2+influx was also stimulated in a dose-dependent manner (50-400 nM) by the amphiphilic peptide melittin. This effect was blocked by the phosphqlipase A2 inhibitor 3-(4-octadecyl)-benzoylacrylic acid. The unsaturated fatty acid AA, in the range of 10-75 ?M, induced Ca2+entry by a mechanism sensitive to LaCb. However, both melittin and AA induced increase in [Ca2+]i in T. brucei procyclic trypomastigotes incubated in Ca2+-free medium implying Ca2+ mobilization trom intracellular stores. This hypothesis was supported by experiments showing that AA promoted Ca2+release from the acidocalcisomes of these cells. The results showing changes in mitochondrial membrane potential, release of acridine orange and Ca2+from the acidocalcisomes and Ca2+release across the plasma membrane suggest that in addition to the stimulation of a Ca2+channel mediated process, AA, in the range of concentrations used here, have other nonspecific effects on the trypanosomatids membranes.

ASSUNTO(S)

tripanossomo mitocondria calcio acidos graxos

ACESSO AO ARTIGO

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