ABSTRACT
OBJECTIVE: We investigated the effect of peroxisome proliferator activator receptors α (PPARα) on cardiomyocyte apoptosis induced by glucose and fatty acid, and if high glucose levels could increase fatty acid-induced apoptosis. METHODS: Cardiomyocytes were maintained in Dulbecco's Modified Eagle Medium and divided into 5 groups: Group N (control Group); Group G (exposed to 25.5 mmol/l glucose); Group L (exposed to 5 mmol/l glucose, fatty acid); Group H (exposed to 25.5 mmol/l glucose and fatty acid); Group I (exposed to 25.5 mmol/l glucose, fatty acid and Wy14643). Apoptosis was detected by terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling. Immunocytochemistry staining detected PPARα's expressing, and western blotting detected PPARα and nuclear factor κB's (NF-κB) protein level. RESULTS: Exposure to fatty acid resulted in a significant increase of cardiomyocytes apoptosis, with the extension of NF-κB formation, whereas exposure to 25.5 mmol/l glucose had no influence on the apoptosis rate. However, combination with fatty acid and high glucose concentration had induced more apoptosis with the up-regulation of NF-κB formation. The fatty acid and glucose-induced effects were improved by Wy14643, with down-regulation of NF-κB formation. CONCLUSION: These results suggested that in neonatal cardiomyocytes, fatty acid and glucose in combination with fatty acid induced apoptosis via NF-κB formation and activation of apoptosis pathways; glucose in combination with fatty acid induce more apoptosis rate for the more NF- κB formation, activation of the PPARα can reverse such apoptosis effect. The results also suggest that gluco-lipotoxicity may play a central role in the development of diabetic cardiomyopathy, and PPARα-agonist may be an effective drug in treating the diabetic cardiomyopathy.
