Hypertrophied cardiomyocytes demonstrated resistance to HNE-induced cell death, characterized by a 2-fold increase in glycolysis and increased oxidation of HNE to 4-hydroxynonenoic acid.
Does phenylephrine-induced hypertrophy alter the bioenergetic response and survival of neonatal rat cardiomyocytes exposed to electrophilic stress?
Hypertrophied cardiomyocytes exhibit a protected phenotype against electrophilic stress through enhanced glycolysis and electrophile metabolism, suggesting a compensatory bioenergetic adaptation during early cardiac remodeling.
During cardiac remodelling, the heart generates higher levels of reactive species; yet an intermediate 'compensatory' stage of hypertrophy is associated with a greater ability to withstand oxidative stress. The mechanisms underlying this protected myocardial phenotype are poorly understood. We examined how a cellular model of hypertrophy deals with electrophilic insults, such as would occur upon ischaemia or in the failing heart. For this, we measured energetics in control and PE (phenylephrine)-treated NRCMs (neonatal rat cardiomyocytes) under basal conditions and when stressed with HNE (4-hydroxynonenal). PE treatment caused hypertrophy as indicated by augmented atrial natriuretic peptide and increased cellular protein content. Hypertrophied myocytes demonstrated a 2.5-fold increase in ATP-linked oxygen consumption and a robust augmentation of oligomycin-stimulated glycolytic flux and lactate production. Hypertrophied myocytes displayed a protected phenotype that was resistant to HNE-induced cell death and a unique bioenergetic response characterized by a delayed and abrogated rate of oxygen consumption and a 2-fold increase in glycolysis upon HNE exposure. This augmentation of glycolytic flux was not due to increased glucose uptake, suggesting that electrophile stress results in utilization of intracellular glycogen stores to support the increased energy demand. Hypertrophied myocytes also had an increased propensity to oxidize HNE to 4-hydroxynonenoic acid and sustained less protein damage due to acute HNE insults. Inhibition of aldehyde dehydrogenase resulted in bioenergetic collapse when myocytes were challenged with HNE. The integration of electrophile metabolism with glycolytic and mitochondrial energy production appears to be important for maintaining myocyte homoeostasis under conditions of increased oxidative stress.
Sansbury et al. (Thu,) conducted a other in Cardiac hypertrophy and oxidative stress. Phenylephrine (PE)-induced hypertrophy and 4-hydroxynonenal (HNE) stress vs. Control neonatal rat cardiomyocytes was evaluated on Energetics, cell death, and electrophile metabolism. Hypertrophied cardiomyocytes demonstrated resistance to HNE-induced cell death, characterized by a 2-fold increase in glycolysis and increased oxidation of HNE to 4-hydroxynonenoic acid.