glutaminase and Heart-Failure

Metabolic remodeling in cardiomyocytes is deeply associated with the pathogenesis of heart failure (HF). Glutaminolysis is an anaplerotic pathway that incorporates α-ketoglutarate (αKG) derived from glutamine into the tricarboxylic acid (TCA) cycle. It is well known that cancer cells depend on glutamine for their increased energy demand and proliferation; however, the physiological roles of glutamine metabolism in failing hearts remain unclear.. To investigate the regulatory mechanisms and biological effects of glutamine metabolism in oxidative stress-induced failing myocardium.. The intracellular levels of glutamine, glutamate, and αKG were significantly decreased by H. Our study demonstrates that under oxidative stress, glutaminolysis is upregulated to compensate for the loss of αKG and its replenishment into the TCA cycle, thereby exerting cardioprotective effects by maintaining ATP and GSH levels. Modulation of glutamine metabolism in failing hearts might provide a new therapeutic strategy for HF.

Topics: Animals; Animals, Newborn; Cell Survival; Cells, Cultured; Citric Acid Cycle; Energy Metabolism; Glutamic Acid; Glutaminase; Glutamine; Heart Failure; Ketoglutaric Acids; Metabolic Networks and Pathways; Myocytes, Cardiac; Oxidative Stress; Rats