INVESTIGADORES
PODEROSO Juan Jose
congresos y reuniones científicas
Título:
Mitochondrial translocation of inducible nitric oxide synthase as a mechanism of mitochondrial nitrosative damage in endotoxemia
Autor/es:
CARRERAS MC; ANTICO ARCIUCH V; FRANCO MC; FINOCCHIETTO P; PERALTA JG; PODEROSO JJ
Lugar:
Buenos Aires
Reunión:
Congreso; XII Biennial Meeting of the Society for Free Radical Research International.; 2004
Institución organizadora:
Society for Free Radical Research International.
Resumen:
Nitric oxide (NO) is one of the endogenous mediators of sepsis, a systemic inflammatory response induced by severe infection or endotoxemia. Lately, the impairment of mitochondrial function has been related to the pathogenesis of sepsis. In this context, the aim of this study was: to examine NOS expression in mitochondria and its effects on mitochondrial function in endotoxemia. Adult Wistar rats were treated with 10 mg/kg LPS for 2 to 24 h and liver was excised for the evaluation of  mRNA and protein expression of NOS isoforms. Mitochondrial damage was evaluated by respiratory complex activities. Decreased constitutive Ca2+-dependent mtNOS activity and expression paralleled the appearance of Ca2+-independent iNOS into mitochondria after 4-6 h of LPS administration. iNOS mRNA was detectable after 2 h, maximal at 4h and progressively decreased up to 24 h where it was not detectable. Neuronal NOS mRNA obtained by nested PCR was oppositely modulated. The increase of intramitochondrial NO production was followed by nitration of mitochondrial proteins and inhibition of mitochondrial complex I activity at 12 h. In these terms, the potential modulation of intracellular trafficking of iNOS to the mitochondria would be important in the control of mitochondrial damage by NO and reactive nitrogen species.