Objective: FoxO1 acts as a pivotal transcription factor in insulin signaling. However, in hyperglycemia induced cardiac complications, whether FoxO1 is involved remains unclear. The goal of this study was to delineate the potential role of FoxO1 under high-glucose condition.
Materials/methods: We investigated insulin resistance and reactive oxygen species (ROS) generation in H9c2 cardiomyoblasts after high-glucose exposure. A series of autophagy biomarkers were measured and further confirmed by LC3 turnover assay. Using gene silencing and overexpression experiments we dissected the molecular mechanisms of FoxO1 regulated autophagy. We also tested the protective effect of (-)-epigallocatechin-3-gallate (EGCG, a green tea-derived polyphenol) in high-glucose treated H9c2 cardiomyoblasts.
Results: High-glucose elicited elevated ROS, autophagy and FoxO1 abundance in cultured H9c2 cardiomyoblasts. Specifically, high-glucose significantly augmented the acetylated FoxO1 in cytosol. In line, compared with 3A-FoxO1 (majorly localized in nuclei with a strong transcriptional activity), overexpression of WT-FoxO1 led to more intense elevated autophagy with enhanced acetylation of FoxO1. In addition, FoxO1 RNAi brought down autophagy induced by high-glucose. Intriguingly, EGCG successfully reversed ROS, autophagy and acetylated FoxO1 in high-glucose treated H9c2 cells.
Conclusion: Our findings suggest that FoxO1, especially the acetylated form, regulates high-glucose induced autophagy in H9c2 cardiomyoblasts, which can be prevented by EGCG via a possible ROS-FoxO1 pathway.
Keywords: Autophagy; Cardiomyoblasts; EGCG; FoxO1; High-glucose.
Copyright © 2014 Elsevier Inc. All rights reserved.