Introduction
NADP(H) redox couple as cofactor/electron carrier in cardiommyocytes
NADPH is an essential cofactor of glutathione reductase (GR) and thioredoxin reductase (TRs) in cardiommyocytes, with a crucial role in maintaining cellular redox homeostasis and energy metabolism. GR catalyzes the recycling of Glutathion (GSH) from oxidized glutathione (GSSG), and TRs reduces oxidized Trx-S2 into Trx-(SH)2. Simultaneously, both enzymes require NADPH as an electron donor and oxidize it to NADP+. Once O2• − is formed, for example, from NOXs in the cytosol and from mitochondrial electron transport chain (ETC), cytosolic CuZnSOD and mitochondrial MnSOD will reduce it to H2O2. GSH can be used by glutathione peroxidase (GPx) to reduce H2O2 further to water. Trx-(SH)2 provides reducing equivalents for Prx in the removal of H2O2.
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The connection of NADP(H) with cardiovascular pathologies
NADP(H) plays a dual role in cardiovascular pathologies. On the one hand, the reduced NADPH can result in significant antioxidant deficiencies and intracellular accumulation of free radicals, which triggers lipid peroxidation, inflammation, and vascular dysfunction, ultimately exacerbating the course of atherosclerosisoxidase. On the other hand, high NADPH level can give rise to myocardial injury by inducing reductive stress and enhancing reactive oxygen species (ROS) production.
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Conclusion
Changes in cellular NADP(H) content affect the intermediary metabolism of cardiac function, especially in diseased myocardium. Maintaining the balance between NADP+ and NADPH in cardiommyocytes is critically important for the treatment of CVD. Either deficiency or excess NADP(H) levels can lead to imbalances in cellular redox state and metabolic homeostasis, resulting in energy stress, redox stress, and ultimately disease state. NADP(H) has an important therapeutic value in CVD.
Reference
Sun Y, Wu D, Hu Q. NADP+/NADPH in Metabolism and its Relation to Cardiovascular Pathologies. Curr Med Chem. Published online February 16, 2024. doi:10.2174/0109298673275187231121054541
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