INVESTIGADORES
ALVAREZ Silvia
artículos
Título:
Cardiac mitochondrial biogenesis in endotoxemia is not accompanied by mitochondrial function recovery
Autor/es:
VANASCO, VIRGINIA; SAEZ, TRINIDAD; MAGNANI, NATALIA; PEREYRA, LEONARDO; MARCHINI, TIMOTEO; CORACH, ALEJANDRA; VACCARO, M. INÉS; CORACH, DANIEL; EVELSON, PABLO; ALVAREZ, SILVIA
Revista:
FREE RADICAL BIOLOGY AND MEDICINE
Editorial:
ELSEVIER SCIENCE INC
Referencias:
Lugar: Amsterdam; Año: 2014 vol. 77 p. 1 - 9
ISSN:
0891-5849
Resumen:
Mitochondrial biogenesis emerges
as a compensatory mechanism involved in the recovery process in endotoxemia and
sepsis. The aim of this work was to analyze the time course of cardiac
mitochondrial biogenesis process occurring during endotoxemia, with emphasis in
the quantitative analysis of mitochondrial function. Female Sprague-Dawley rats
(45 days old) were ip injected with LPS (10 mg/kg). Measurements were performed
at 0-24h after LPS administration. PGC-1α and mtTFA expression for biogenesis, and p62 and LC3
expression for autophagy, were analyzed by western blot; mitochondrial DNA
levels by qPCR, and mitochondrial morphology by transmission electron
microscopy. Mitochondrial function was evaluated as
oxygen consumption and respiratory chain complexes activity. PGC-1α and mtTFA expression resulted significantly increased in every
time-point analyzed, and mitochondrial mass was observed increased by 20%
(p<0.05) at 24h. p62 expression was found significantly decreased in a
time-dependent manner. LC3-II expression was observed significantly increased
at all-time points analyzed. Ultrastructurally, mitochondria displayed several
abnormalities (internal vesicles, cristae disruption, and swelling) at 6 and
18h. Structures compatible with fusion/fission processes were observed at 24 h.
Significant decrease in state 3 respiration was observed in every time-point
analyzed (LPS 6h: 20%, p<0.05). Mitochondrial complex I activity was found
decreased by 30% in LPS-treated animals at 6 and 24h. Complex II and complex IV
showed decreased activity only at 24h. The present results show
that partial restoration
of cardiac mitochondrial architecture is not accompanied by improvement of
mitochondrial function in acute endotoxemia. The key implication of our study
is that cardiac failure due to bioenergetic dysfunction will be overcome by
therapeutic interventions aimed to restore cardiac mitochondrial function.