t0901317 and Diabetic-Cardiomyopathies

The aim of the present study was to investigate the protective effects of T0901317 (T0), a potent agonist of liver X receptors (LXRs), on high glucose-induced oxidative stress and apoptosis in H9c2 cardiac cells. Exposure of H9c2 cells to high glucose alone, not only caused a significant increase in apoptosis and reactive oxygen species (ROS) generation, but also led to a decrease in mitochondrial membrane potential (ΔΨm), release of cytochrome c, decrease in Bcl-2, increase in Bax expression and the activation of caspase-3, caspase-9, poly (ADP-ribose) polymerase (PARP) and nuclear factor (NF)-κB. However, pretreatment with T0 effectively decreased apoptosis, reduced the levels of ROS, abrogated ΔΨm, inhibited cytochrome c release and NF-κB activation, increased Bcl-2 and decreased Bax expression. In conclusion, our data suggest that T0 exerts protective effects against high glucose-induced apoptosis in H9C2 cardiac muscle cells via inhibition of ROS production, mitochondrial death and NF-κB activation.

Topics: Animals; Apoptosis; Cell Line; Diabetic Cardiomyopathies; Glucose; Hydrocarbons, Fluorinated; Liver X Receptors; Membrane Potential, Mitochondrial; Mitochondria, Heart; Myocytes, Cardiac; NF-kappa B; Orphan Nuclear Receptors; Oxidative Stress; Promoter Regions, Genetic; Protein Binding; Rats; Reactive Oxygen Species; Sulfonamides; Transcriptional Activation