Retinol induces permeability transition and cytochrome c release from rat liver mitochondria.
Biological actions of retinoids on modulation of cellular gene expression by nuclear receptors are widely known. Recently, extra-nuclear effects of retinoids have been proposed, but remain to be better elucidated. Considering that retinoids induce apoptosis in tumor cells by an unknown mechanism, and that mitochondria play a key role in controlling apoptosis via cytochrome c (cyt c) release, we exposed rat liver mitochondria to 3-40 microM of retinol (vitamin A), and observed that retinol causes mitochondrial permeability transition (MPT) and cyt c release, in a concentration-dependent pattern. Increased superoxide anion generation and lipoperoxidation were also observed. Cyclosporin A or trolox co-administration reverted all parameters tested. In view of these findings, we conclude that retinol induces mitochondria oxidative damage, leading to MPT and cyt c release by opening of the permeability transition pore, thus suggesting a putative mechanism of apoptosis activation by retinol.
Klamt
Fábio
F
Centro de Estudos em Estresse Oxidativo, Departamento de Bioquímica, ICBS/Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, Brazil. fklamt@terra.com.br
Roberto de Oliveira
Marcos
M
Moreira
José Cláudio Fonseca
JC
D000704:Analysis of Variance; D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D045304:Cytochromes c / Q000378:metabolism*; D015227:Lipid Peroxidation / Q000187:drug effects; D008099:Liver / Q000187:drug effects / Q000502:physiology*; D008564:Membrane Potentials / Q000187:drug effects*; D046529:Microscopy, Electron, Transmission; D008928:Mitochondria / Q000502:physiology* / Q000648:ultrastructure; D018384:Oxidative Stress / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D013481:Superoxides / Q000378:metabolism; D014801:Vitamin A / Q000494:pharmacology*
D013481:Superoxides; D014801:Vitamin A; D045304:Cytochromes c