Cardioprotective strategies preserve the stability of respiratory chain supercomplexes and reduce oxidative stress in reperfused ischemic hearts.

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.

Uncoupling Protein Overexpression in Metabolic Disease and the Risk of Uncontrolled Cell Proliferation and Tumorigenesis.

In metabolic diseases such as obesity, metabolic syndrome and type II diabetes, the over-expression of uncoupling proteins (UCPs) in a response to increased reactive oxygen species (ROS) generation by mitochondrial respiratory complexes, and to the excess of free fatty acid (FFA) supply from adipose tissue, may protect cells from oxidative stress, lipotoxicity and in turn from death. UCPs by reducing superoxide anion and H2O2 generation trigger several signals to cell for their adaptation to the lipotoxic microenvironment. In mitochondria, a decrease of cytochrome c (cyt c) and proapoptotic protein release promotes cell survival and proliferation. The altered lipid metabolism also affects cardiolipin susceptibility to the peroxidation, a process involved in the dissociation of cyt c from mitochondrial inner membrane and its release, a key step of apoptosis. Therefore, UCPs by attenuating ROS generation and lipotoxicity may downregulate programmed cell death, a well-known physiological process controlling cell proliferation contributing to uncontrolled cell proliferation and tumorigenesis. In addition, tumor cells over-expressed UCPs, by inhibiting ROS generation acquire resistance to death during pharmacological treatment with oxidative stress drug inducers. Therefore, the aim of this review is to discuss recent findings regarding the role that UCPs play in cell survival by protecting against ROS generation and maintaining bioenergetic metabolism homeostasis to promote cell proliferation.

Effect of an avocado oil-rich diet over an angiotensin II-induced blood pressure response.

We studied the effect of an avocado oil-rich diet on (1) the blood pressure response to angiotensin II (AngII) and (2) the fatty acid composition of cardiac and renal membranes on male Wistar rats. The avocado oil-rich diet induced a slightly higher AngII-induced blood pressure response in the rats as compared to the control rats. In cardiac microsomes, avocado oil induced an increase in oleic acid content (13.18+/-0.33% versus 15.46+/-0.59%), while in renal microsomes, the oil decreased alpha-linolenic acid content (0.34+/-0.02% versus 0.16+/-0.12%), but increased the arachidonic acid proportion (24.02+/-0.54% versus 26.25+/-0.54%), compared to control. In conclusion, avocado oil-rich diet modifies the fatty acid content in cardiac and renal membranes in a tissue-specific manner. The rise in renal arachidonic acid suggests that diet content can be a key factor in vascular responses.