Mitochondrial permeability transition and cytochrome c release induced by selenite.
Cytochrome c release and mitochondrial permeability transition (MPT) play important roles in apoptosis. In this study, we found that selenium, an essential trace element, induced mitochondrial membrane potential (Delta psi(m)) loss, swelling, and cytochrome c release in isolated mitochondria. All of the above observations were blocked by cyclosporin A (CsA), which is a specific inhibitor to permeability transition pore (PTP), indicating selenite-induced mitochondrial changes were mediated through the opening of PTP. In physiological concentration, selenite could induce mitochondria at low-conductance PTP 'open' probability, which is correlated to regulate the physiological function, whereas in toxic concentration, induce mitochondria at high-conductance PTP 'open' probability and rapidly undergo a process of osmotic swelling following diffusion toward matrix as for inducer (Ca(2+)/P(i)). Selenite also induced other mitochondrial marker enzymes including monoamine oxidase (MAO) and mitochondria aspartate aminotransferase (mAST). Oligomycin inhibited the selenite-induced cytochrome c release and Delta psi(m) loss, showing that F(0)F(1)-ATPase was important in selenite or Ca(2+)/P(i)-induced MPT.
Zhu
Yushan
Y
Institute of Pharmacy, Huazhong University of Science and Technology, 430074, Wuhan, PR China. zhuyushan01@sina.com
Xu
Huibi
H
Huang
Kaixun
K
D000818:Animals; D017209:Apoptosis; D001219:Aspartate Aminotransferases / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D016572:Cyclosporine / Q000494:pharmacology; D003574:Cytochrome c Group / Q000378:metabolism*; D066298:In Vitro Techniques; D008564:Membrane Potentials / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism*; D008995:Monoamine Oxidase / Q000378:metabolism; D010179:Pancreas / Q000187:drug effects / Q000378:metabolism; D010539:Permeability / Q000187:drug effects; D010710:Phosphates / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D018038:Sodium Selenite / Q000494:pharmacology*
D003574:Cytochrome c Group; D010710:Phosphates; D016572:Cyclosporine; D008995:Monoamine Oxidase; D001219:Aspartate Aminotransferases; D018038:Sodium Selenite; D002118:Calcium