Suramin inhibits respiration and induces membrane permeability transition in isolated rat liver mitochondria.
Suramin, a polysulfonated naphthylamine, caused a dose dependent inhibition of carbonyl cyanide p-(tri-fluoromethoxy)phenylhydrazone-stimulated respiration supported either by succinate or a cocktail of alphaketoglutarate, malate and isocitrate in isolated rat liver mitochondria. The half-maximum effect was obtained at 40 and 140 microM suramin for NADH- or FADH(2)-linked substrates, respectively. The respiration supported by N,N,N'N'-tetramethyl-p-phenylenediamine oxidation was unaffected by suramin (<or=500 microM). The latter respiratory substrate was used in the studies at examining the effects of suramin on the permeability properties of the inner mitochondrial membrane. These experiments provided evidence that suramin causes Ca(2+)-dependent mitochondrial swelling sensitive to the mitochondrial permeability transition (MPT) inhibitors cyclosporin A, ADP and Mg(2+). In addition, suramin decreased the content of reduced mitochondrial membrane protein thiols suggesting that thiol oxidation is the mechanism underlying suramin-induced MPT.
Bernardes
C F
CF
Departamento de Patologia Clínica, Faculdade de Ciências Médicas, Universidade Estadual de Campinas, Campinas, SP 13083-970, Brazil. mfagian@obelix.unicamp.br
Fagian
M M
MM
Meyer-Fernandes
J R
JR
Castilho
R F
RF
Vercesi
A E
AE
D000244:Adenosine Diphosphate / Q000494:pharmacology; D000818:Animals; D002259:Carbonyl Cyanide p-Trifluoromethoxyphenylhydrazone / Q000037:antagonists & inhibitors / Q000494:pharmacology; D002463:Cell Membrane Permeability / Q000187:drug effects*; D019069:Cell Respiration / Q000187:drug effects*; D002614:Chelating Agents / Q000494:pharmacology; D016572:Cyclosporine / Q000494:pharmacology; D004347:Drug Interactions; D004533:Egtazic Acid / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005033:Ethylmaleimide / Q000494:pharmacology; D007425:Intracellular Membranes / Q000187:drug effects / Q000502:physiology; D008274:Magnesium / Q000494:pharmacology; D008564:Membrane Potentials / Q000187:drug effects; D008930:Mitochondria, Liver / Q000187:drug effects* / Q000378:metabolism; D008933:Mitochondrial Swelling / Q000187:drug effects; D010101:Oxygen Consumption / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D013439:Sulfhydryl Reagents / Q000494:pharmacology; D013498:Suramin / Q000633:toxicity*; D014344:Trypanocidal Agents / Q000633:toxicity*
D002614:Chelating Agents; D004791:Enzyme Inhibitors; D013439:Sulfhydryl Reagents; D014344:Trypanocidal Agents; D002259:Carbonyl Cyanide p-Trifluoromethoxyphenylhydrazone; D004533:Egtazic Acid; D013498:Suramin; D000244:Adenosine Diphosphate; D016572:Cyclosporine; D008274:Magnesium; D005033:Ethylmaleimide