INVESTIGADORES
EVELSON Pablo Andres
congresos y reuniones científicas
Título:
Endotoxemia impairs heart mitochondrial function by decreasing ATP bioavailability and mitochondrial complex I activity
Autor/es:
VANASCO, VIRGINIA; CARRIVALE, ANA; EVELSON, PABLO; BOVERIS, ALBERTO; ALVAREZ, SILVIA
Lugar:
Sao Pedro
Reunión:
Congreso; VII Meeting of the Society for Free Radical Biology and Medicine South American Group; 2011
Institución organizadora:
Society for Free Radical Biology and Medicine South American Group
Resumen:
Although
the precise mechanism by which sepsis leads to organ dysfunction has not been
yet clarified, several authors addressed the relevance of mitochondrial
function during endotoxemia and sepsis, as it may play a role in the genesis of
the tissue injury described in these syndromes. This work is focused on the mechanism of
mitochondrial bioenergetic dysfunction in heart in an acute model of
endotoxemia induced in female
Sprague Dowley rats (45 days) by LPS (10 mg/kg ip). Assays were performed in
heart 6h after the treatment. We analyzed pathways of tissue O2
uptake as mitochondrial O2 consumption and NADPH oxidase activity.
In mitochondria, NO, H2O2 and O2-
production were measured. Finally, we determined ATP bioavailability and
production rate, and membrane potential. The ratio between O2
consumed by mitochondria and by non-mitochondrial pathways decreased by 25% in
LPS-animals compared to control animals. This observation may be due to a
2-fold increase in NADPH oxidase activity found in LPS-animals (control: 13250
± 3020 cpm/mg tissue, p <0.05). Mitochondrial complex I activity and mitochondrial
O2 consumption were found impaired and ATP levels and production by
FoF1 ATP synthase were found decreased, while no changes
were observed in mitochondrial membrane potential. This scenario is accompanied by 65% increased production of O2-
(control: 2.34 ± 0.25 nmol/min mg protein, p < 0.0001) and 20% of H2O2
(value control: 1.17 ± 0.13 nmol/min mg protein, p < 0.0001) probably by
electron-leackage. Increased NO production possitively correlated to mtNOS
functional activity. We suggest that bioenergetic impairment observed in heart
endotoxemia is mainly due to impairment of ATP bioavailability and oxygen
consumption through complex I inhibition without affecting mitochondrial
membrane potential.