Abstract
We have developed and characterized a model of isoproterenol (ISO)-induced myocardial necrosis, identifying three stages of cardiac damage: a pre-infarction (0–12 h), infarction (24 h), and post-infarction period (48–96 h). Using this model, we have previously found alterations in calcium homeostasis and their relationship with oxidant stress in mitochondria, which showed deficient oxygen consumption and coupled ATP synthesis. Therefore, the present study was aimed at assessing the mitochondrial ability to transport and oxidize cytoplasmic reducing equivalents (NADH), correlating the kinetic parameters of the malate-aspartate shuttle, oxidant stress, and mitochondrial functionality. Our results showed only discreet effects during the cardiotoxic ISO action on the endogenous malate-aspartate shuttle activity, suggesting that endogenous mitochondrial NADH oxidation capacity (Nohl dehydrogenase) was not affected by the cellular stress. On the contrary, the reconstituted system showed significant enhancement in maximal capacity of the malate-aspartate shuttle activity only at later times (post-infarction period), probably as a compensatory part of cardiomyocytes’ response to the metabolic and functional consequences of the infarcted tissue. Therefore, these findings support the notion that heart damage associated with myocardial infarction suffers a set of sequential biochemical and metabolic modifications within cardiomyocytes, where mitochondrial activity, controlling the redox state, could play a relevant role.
Highlights
Tissues and organs with high oxidative performance, such as the myocardium, are highly dependent on adequate mitochondrial activity
Of three control animals andand fivefive ratsrats treated with perper experimental point of the kinetics of the of three control animals treated with experimental point of the kinetics of the reconstituted malate-aspartate shuttle (MAS)
When we recorded mitochondrial nicotinamide adenine dinucleotide hydrogen (NADH) oxidation after reconstituting the MAS, we found significant changes in these parameters (Figure 5)
Summary
Tissues and organs with high oxidative performance, such as the myocardium, are highly dependent on adequate mitochondrial activity. In conditions of enough O2 availability and full oxidative mitochondrial capacity, the NADH produced by the cytosolic glycolytic pathway can be used by mitochondria only if the shuttle systems are functional. These biochemical pathways involve the reduction of the substrate in the cytosol that are permeable to the mitochondrial inner membrane. These substrates are oxidized by the mitochondrion to yield a substrate that can return to the cytosol for a new reduction. The principal system is the malate-aspartate shuttle (MAS) since the glycerol-phosphate shuttle is almost undetectable [2]
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
