title: Hypothyroidism provides resistance to kidney mitochondria against the injury induced by renal ischemia-reperfusion.
abstract: 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.
authors.affiliation: Departamento de Bioquímica, Instituto Nacional de Cardiología, Ignacio Chávez, Tlalpan, DF 014080, México.
authors.forename: Cecilia
authors.initials: C
authors.lastname: Zazueta
authors.forename: Martha
authors.initials: M
authors.lastname: Franco
authors.forename: Francisco
authors.initials: F
authors.lastname: Correa
authors.forename: Noemí
authors.initials: N
authors.lastname: García
authors.forename: José
authors.initials: J
authors.lastname: Santamaría
authors.forename: Eduardo
authors.initials: E
authors.lastname: Martínez-Abundis
authors.forename: Edmundo
authors.initials: E
authors.lastname: Chávez
mesh_terms: 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
chemical_list: 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