Autophagy Induction in AC‐16 Human Cardiomyocytes: Effects of Resveratrol and Rapamycin (LB835)

Mitochondrial dysfunction and increased oxidative stress contribute to the deterioration of cardiomyocyte and heart function with advancing age. Autophagy is the process by which damaged mitochondria are removed from cells. Increasing autophagy may help reverse some detrimental effects of aging on the heart. We tested the hypothesis that resveratrol, a plant polyphenol, and rapamycin, an immunosuppressant, will induce autophagy in the AC‐16 human cardiomyocytes (AC‐16 HC) independently and in combination will produce synergistic and/or additive effects. AC‐16 HC cells were incubated for 24 hours with resveratrol (50uM), rapamycin (1uM) and a 1:1 combination of the two treatments. Induction of autophagy was assessed by protein concentration and western blot analysis using the autophagy indicator LC3B antibody. ImageLab densitometry software was used to assess the band intensity. Treatment of the cells with the respective concentrations of resveratrol and rapamycin resulted in the up‐regulation of autophagy in the AC‐16 HC cells. The combination approach showed a modest upregualtion, but there was no significant synergistic effect. Taken together, resveratrol and rapamycin independently and in combination have up‐regulated autophagy in the AC‐16 HC cells. The dose response of resveratrol and rampamycin on the induction of autophagy and the optimum functional or physiological concentration required for in‐vivo changes remain to be determined. The optimum exposure time coursemust also be determined to optimize the duration of increased autophagy flux. Future studies are needed to optimize and fully understand the role of resveratrol and rampamycin through autophagy in human cardiomyocytes. Grant Funding Source : Supported by: HHMI‐Science for Life Program and NIH/NIA P30 AG028740