Cardioprotective strategies preserve the stability of respiratory chain supercomplexes and reduce oxidative stress in reperfused ischemic hearts
Por:
Ramirez-Camacho, I., Correa, F., El Hafidi, M., Silva-Palacios, A., Ostolga-Chavarria, M., Esparza-Perusquia, M., Olvera-Sanchez, S., Flores-Herrera, O., Zazueta, C.
Publicada:
1 dic 2018
Resumen:
Electron leakage from dysfunctional respiratory chain and consequent
superoxide formation leads to mitochondrial and cell injury during
ischemia and reperfusion (IR). In this work we evaluate if the
supramolecular assembly of the respiratory complexes into supercomplexes
(SCs) is associated with preserved energy efficiency and diminished
oxidative stress in post-ischemic hearts treated with the antioxidant
N-acetylcysteine (NAC) and the cardioprotective maneuver of
Postconditioning (PostC). Hemodynamic variables, infarct size, oxidative
stress markers, oxygen consumption and the activity/stability of SCs
were compared between groups. We found that mitochondrial oxygen
consumption and the activity of respiratory complexes are preserved in
mitochondria from reperfused hearts treated with both NAC and PostC.
Both treatments contribute to recover the activity of individual
complexes. NAC reduced oxidative stress and maintained SCs assemblies
containing Complex I, Complex III, Complex IV and the adapter protein
SCAFI more effectively than PostC. On the other hand, the activities of
CI, CIII and CIV associated to SCs assemblies were preserved by this
maneuver, suggesting that the activation of other cardioprotective
mechanisms besides oxidative stress contention might participate in
maintaining the activity of the mitochondrial respiratory complexes in
such superstructures.
We conclude that both the monomeric and the SCs assembly of the
respiratory chain contribute to the in vivo functionality of the
mitochondria. However, although the ROS-induced damage and the
consequent increased production of ROS affect the assembly of SCs, other
levels of regulation as those induced by PostC, might participate in
maintaining the activity of the respiratory complexes in such
superstructures.
Filiaciones:
Departamento de Biomedicina Cardiovascular, Instituto Nacional de Cardiología. I. Ch., Mexico, D.F., 14080, Mexico
Departamento de Bioquímica, Facultad de Medicina, Universidad Nacional Autónoma de México, Mexico, D.F., 04510, Mexico
Inst Nacl Cardiol I Ch, Dept Biomed Cardiovasc, Mexico City 14080, DF, Mexico
Univ Nacl Autonoma Mexico, Dept Bioquim, Fac Med, Mexico City 04510, DF, Mexico
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