Regulación del complejo III mitocondrial por óxido nítrico : aspectos bioquímicos y biofísicos

The aim of this work was to characterize the effects of NO in the ubiquinone:cytochrome b area. The results obtained with GSNO, SPER-NO, NO solution or NO produced endogenously, show that [NO] ? 1.25 ?M (determined electrochemically and spectrophotometrically), inhibit complex II-III activity by blo...

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Autor principal: Iglesias, Darío Ezequiel
Otros Autores: Valdez, Laura B.
Formato: Tesis doctoral acceptedVersion
Lenguaje:Español
Publicado: Facultad de Farmacia y Bioquímica 2018
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Acceso en línea:http://repositoriouba.sisbi.uba.ar/gsdl/cgi-bin/library.cgi?a=d&c=posgraafa&cl=CL1&d=HWA_2604
http://repositoriouba.sisbi.uba.ar/gsdl/collect/posgraafa/index/assoc/HWA_2604.dir/2604.PDF
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Sumario:The aim of this work was to characterize the effects of NO in the ubiquinone:cytochrome b area. The results obtained with GSNO, SPER-NO, NO solution or NO produced endogenously, show that [NO] ? 1.25 ?M (determined electrochemically and spectrophotometrically), inhibit complex II-III activity by blocking the electron transfer at complex III. The accumulation of UQH2 and cytochromes b2+ is in agreement with these observations. The inhibition was insensitive to HbO2 addition and [O2] changes. Hyperbolic increases in O2?- and H2O2 production rates were observed, according to the enhancement in [UQH?]ss. NO inhibited O2 consumption and decreased ?? in coupled mitochondria, by regulation of complexes IV and III activities. The reduction of cytochrome bH by NO allowed to propose it as a probable interaction site. A kinetic model of the bc1 complex inhibited by NO was constructed, which agrees with the experimental results. The intramitochondrial [NO]ss estimated in state 3 (?65 nM) and in state 4 (?370 nM) suggest that NO modulates both complex IV and complex III in physiological conditions. The effects of NO on complex III are antimycin-like.