Hypothyroidism provides resistance to kidney mitochondria against the injury induced by renal ischemia-reperfusion.
Massive Ca(2+) accumulation in mitochondria, plus the stimulating effect of an inducing agent, i.e., oxidative stress, induces the so-called permeability transition, which is characterized by the opening of a nonspecific pore. This work was aimed at studying the influence of thyroid hormone on the opening of such a nonspecific pore in kidney mitochondria, as induced by an oxidative stress. To meet this objective, membrane permeability transition was examined in mitochondria isolated from kidney of euthyroid and hypothyroid rats, after a period of ischemia/reperfusion. It was found that mitochondria from hypothyroid rats were able to retain accumulated Ca(2+) to sustain a transmembrane potential after Ca(2+) addition, as well as to maintain matrix NAD(+) and membrane cytochrome c content. The protective effect of hypothyroidism was clearly opposed to that occurring in ischemic reperfused mitochondria from euthyroid rats. Our findings demonstrate that these mitochondria were unable to preserve selective membrane permeability, except when cyclosporin A was added. It is proposed that the protection is conferred by the low content of cardiolipin found in the inner membrane. This phospholipid is required to switch adenine nucleotide translocase from specific carrier to a non-specific pore.
Zazueta
Cecilia
C
Departamento de Bioquímica, Instituto Nacional de Cardiología, Ignacio Chávez, Tlalpan, DF 014080, México.
Franco
Martha
M
Correa
Francisco
F
García
Noemí
N
Santamaría
José
J
Martínez-Abundis
Eduardo
E
Chávez
Edmundo
E
D000818:Animals; D002118:Calcium / Q000378:metabolism; D002308:Cardiolipins / Q000378:metabolism; D016572:Cyclosporine / Q000494:pharmacology; D045304:Cytochromes c / Q000378:metabolism; D004195:Disease Models, Animal; D007037:Hypothyroidism / Q000378:metabolism*; D007274:Injections, Intraperitoneal; D007668:Kidney / Q000378:metabolism* / Q000473:pathology; D008928:Mitochondria / Q000378:metabolism*; D033681:Mitochondrial Membrane Transport Proteins / Q000187:drug effects / Q000378:metabolism*; D051336:Mitochondrial Membranes / Q000187:drug effects / Q000378:metabolism; D000083162:Mitochondrial Permeability Transition Pore; D009243:NAD / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D015427:Reperfusion Injury / Q000378:metabolism* / Q000473:pathology; D013965:Thyroidectomy; D051028:bcl-2-Associated X Protein / Q000378:metabolism
C494828:Bax protein, rat; D002308:Cardiolipins; D033681:Mitochondrial Membrane Transport Proteins; D000083162:Mitochondrial Permeability Transition Pore; D051028:bcl-2-Associated X Protein; D009243:NAD; D016572:Cyclosporine; D045304:Cytochromes c; D002118:Calcium