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Effects of equisetin on rat liver mitochondria: Evidence for inhibition of substrate anion carriers of the inner membrane
Authors:Tamás König  András Kapus  Balázs Sarkadi
Institution:(1) Department of Biochemistry II, Semmelweis University of Medicine, Budapest, Hungary;(2) Department of Physiology, Semmelweis University of Medicine, Budapest, Hungary;(3) National Institute of Haematology, Blood Transfusion, and Immunology, Budapest, Hungary
Abstract:The effect of equisetin, an antibiotic produced byFusarium equiseti, has been studied on mitochondrial functions (respiration, ATPase, ion transport). Equisetin inhibits the DNP-stimulated ATPase activity of rat liver mitochondria and mitoplasts in a concentration-dependent manner; 50% inhibition is caused by about 8 nmol equisetin/mg protein. The antibiotic is without effect either on the ATPase activity of submitochondrial particles or on the purified F1-ATPase. It inhibits both the ADP- or DNP-activated oxygen uptake by mitochondria in the presence of glutamate + malate or succinate as substrates, but only the ADP-stimulated respiration is inhibited if the electron donors are TMPD + ascorbate. It does not affect the NADH or succinate oxidation of submitochondrial particles. Equisetin inhibits in a concentration-dependent manner the active Ca2+-uptake of mitochondria energized both by ATP or succinate without affecting the Ca2+-uniporter itself. The antibiotic inhibits the ATP-uptake by mitochondria (50% inhibition at about 8 nmol equisetin/mg protein) and the Pi and dicarboxylate carrier. It does not lower the membrane potential at least up to 200 nmol/mg protein concentration. The data presented in this paper indicate that equisetin specifically inhibits the substrate anion carriers of the mitochondrial inner membrane.Abbreviations EGTA ethyleneglycol bis/-aminoethylether/-N, N-tetraacetic acid - DNP 2, 4-dinitrophenol - TMPD N,N,Nprime,Nprime,tetramethyl-p-phenylenediamine - CCP carbonylcyanide-m-chlorophenyl hydrazone - TPP tetraphenyl-phosphonium - Hepes /4,(2-hydroxyethyl)-1-piperazine-ethanesulfonic acid/
Keywords:Respiratory chain  ATPase  substrate anion carriers  equisetin  rat liver mitochondria
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