Changes in calcium-dependent membrane permeability properties in mitochondria of livers from arthritic rats.
The involvement of the mitochondrial permeability transition pore (PTP) in the responses of mitochondria from adjuvant-induced arthritic rats to Ca(2+) addition was investigated. The respiratory activity, the Ca(2+)-induced osmotic swelling and the electrophoretic (45)Ca(2+) uptake were evaluated in the absence and in the presence of cyclosporin A (CsA), a well-known inhibitor of the mitochondrial PTP. The Ca(2+)-induced mitochondrial permeability transition (MPT) process occurred in mitochondria from arthritic rats even in the presence of a low Ca(2+) concentration. Whereas in the normal condition, the Ca(2+)-induced uncoupling of oxidative phosphorylation and osmotic swelling was observed in the presence of 10 or 20 microM Ca(2+) concentration, in the arthritic condition, these events occurred at 1.0 microM concentration. In addition, mitochondria from arthritic rats presented an impaired ability to accumulate (45)Ca(2+). All these effects were completely prevented by the administration of CsA. The results of the present study suggest that the higher sensitivity of mitochondria from arthritic rats to Ca(2+)-induced MPT may be an important factor in the pathogenesis of the arthritis disease.
Silva
Pamelli Maria de Souza
PM
Laboratory of Biological Oxidations, Department of Biochemistry, University of Maringá, Maringá, Brazil.
Tanabe
Eduardo
E
Hermoso
Aparecida Pinto Munhos
AP
Bersani-Amado
Ciomar A
CA
Bracht
Adelar
A
Ishii-Iwamoto
Emy L
EL
Salgueiro-Pagadigorria
Clairce Luzia
CL
D000818:Animals; D001169:Arthritis, Experimental / Q000378:metabolism; D002118:Calcium / Q000494:pharmacology*; D002463:Cell Membrane Permeability / Q000187:drug effects*; D016572:Cyclosporine / Q000494:pharmacology; D007425:Intracellular Membranes / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008930:Mitochondria, Liver / Q000187:drug effects* / Q000378:metabolism; D008933:Mitochondrial Swelling; D010100:Oxygen / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
D016572:Cyclosporine; D010100:Oxygen; D002118:Calcium