Cyclosporin A inhibits UV-radiation-induced membrane damage but is unable to inhibit carboxyatractyloside-induced permeability transition.
This work was undertaken to gain further information on the chemical characteristics of the membrane entity involved in the formation of the nonspecific pore. Mitochondria were subjected to oxidative stress by exposure to UV radiation. The results indicate that ultraviolet C radiation induces structural modifications in the adenine nucleotide translocase that lead to membrane permeability transition. Membrane leakage was assessed by measuring mitochondrial Ca2+ transport, the transmembrane electric gradient, and mitochondrial swelling. UV-irradiated mitochondria were unable to retain matrix Ca2+ or to maintain a high level of membrane potential when Ca2+ was added; furthermore, UV-irradiated mitochondria underwent large amplitude swelling. Release of cytochrome c and formation of malondialdehyde, owing to lipid peroxidation, were also seen. Structural modifications of the translocase were revealed by an increase in the binding of the fluorescent probe eosin-5-maleimide to thiol residues of the ADP/ATP carrier. These modifications, taken together with findings indicating that cyclosporin resulted unable to inhibit carboxyatractyloside-induced permeability transition, prompted us to conclude that the translocase could constitute the nonspecific pore or at least be an important modulator of it.
García
Noemí
N
Departamento de Bioquímica, Instituto Nacional de Cardiología, Ignacio Chávez, Mexico, D.F. 014080, Mexico.
Zazueta
Cecilia
C
El-Hafidi
Mohammed
M
Pavón
Natalia
N
Martínez-Abundis
Eduardo
E
Hernández-Esquivel
Luz
L
Chávez
Edmundo
E
D000818:Animals; D001278:Atractyloside / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors / Q000494:pharmacology; D002463:Cell Membrane Permeability / Q000187:drug effects*; D016572:Cyclosporine / Q000494:pharmacology*; D013058:Mass Spectrometry; D051381:Rats; D014466:Ultraviolet Rays
D001278:Atractyloside; D016572:Cyclosporine; C003853:carboxyatractyloside