Pitavastatin attenuates AGEs-induced mitophagy via inhibition of ROS generation in the mitochondria of cardiomyocytes

Abstract

This study aimed to investigate whether pitavastatin protected against injury induced by advanced glycation end products products (AGEs) in neonatal rat cardiomyocytes, and to examine the underlying mechanisms. Cardiomyocytes of neonatal rats were incubated for 48 hours with AGEs (100 mg/mL), receptor for advanced glycation end products (RAGE), antibody (1 mg/mL) and pitavastatin (600 ng/mL). The levels of p62 and beclin1 were determined by Western blotting. Mitochondrial membrane potential (DYm) and the generation of reactive oxygen species (ROS) were measured through the JC-1 and DCFH-DA. In the AGEs group, the expression of beclin1 was remarkably increased compared to the control group, while the expression of p62 was significantly decreased. AGEs also markedly decreased DYm and significantly increased ROS compared with the control group. After treatment with RAGE antibody or pitavastatin, the level of beclin1 was markedly decreased compared with the AGEs group, but the level of p62 was remarkably increased. In the AGEs+ RAGE antibody group and AGEs+ pitavastatin group, DYm was significantly increased and ROS was remarkably decreased compared with the AGEs group. In conclusion, AGEs-RAGE may induce autophagy of cardiomyocytes by generation of ROS and pitavastatin could protect against AGEs-induced injury against cardiomyocytes.

Keywords

advanced glycation end products (AGEs) / receptor for advanced glycation end products (RAGE) / pitavastatin / autophagy / mitochondrial oxidation / oxidative stress

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Acknowledgments

This work was supported by the National Natural Science Foundation of China (NSFC 81570328, Wang Junhong) and the "Sixth-Peak Talent" of Jiangsu Province (2011WSN-029 to Prof. Guo Yan and 2013WSN-036 to Dr. Wang Junhong). Prof. Guo Yan was also support by the Health Department of Jiangsu Province (z201301)

RIGHTS & PERMISSIONS

2017 2017 by the Journal of Biomedical Research.