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

 

Authors: Zhimin Zha1, Junhong Wang1,2, Shiling Li1, Yan Guo1,3

 

Institutions: 1Department of Gerontology, the First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, China; 2Department of Cardiology, the First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, China; 3Department of Cardioangiology, Shengze Hospital of Jiangsu Province, Suzhou, China.

 

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

 

Full Text: JBR-2016-0116.pdf

 

J Biomed Res published on16 April 2017, doi:10.7555/JBR.31.20160116