Wen JJ, et al. - In view of the observations that burn-induced cardiac dysfunction development prominently involve mitochondrial oxidative stress and that AMP-activated kinase (AMPK), an energy sensor, has a principal role in the pathogenesis of heart failure, researchers sought to determine the role of AMPK in cardiac dysfunction after burn injury. It is hypothesized that the AMPK-SIRT1(Sirtuin 1)-PGC1α(Peroxisome proliferator-activated receptor-γ coactivator-1α)-NFE2L2(nuclear factor erythroid 2-related factor 2)-ARE(antioxidant response element) signaling pathway is involved in burn injury through which it results in cardiac mitochondrial impairment, resulting in cardiac dysfunction. They assigned male Sprague Dawley rats to either sham procedure or 60% total body surface area full-thickness burn and performed echocardiograms on them 24-hour post burn. The echocardiogram exhibited development of cardiac dysfunction following burn injury. Biochemistry/molecular biological analysis on heart tissue harvested at 24 hours post burn revealed suppression of cardiac AMPK, SIRT1, and PGC1 expression, which resulted in acetylation of cardiomyocyte proteins post burn. In addition, they identified a decrease in NFE2L2 and NFE2L2 regulated antioxidants (HO-1, NADH quinone oxidoreductase 1, glutamatecysteine ligase catalytic subunit, MnSOD and glutathione peroxidase) post burn, that resulted in cardiac oxidative stress. In vitro, AMPK1 activator and PGC1α agonist treatment led to improvement in Ac16 cell mitochondrial dysfunction, while there was a worsening of Ac16 cellular damage following AMPK1 inhibitor treatment. Findings here suggest the involvement of the AMPK-SIRT1-PGC1α-NFE2L2-ARE signaling pathway in burn-induced cardiac dysfunction and cardiac mitochondrial damage. Further, AMPK and PGC1α agonists are suggested to be valuable as promising therapeutic agents for reversion of cardiac dysfunction after burn injury.