Matrine Protects Cardiomyocytes Against Hyperglycemic Stress by Promoting Mitofusin 2-Induced Mitochondrial Fusion.

Tong Xiao,Yuan Liu,Manman Wei,Jie Huang,Yujie Zhao

doi:10.3389/fphys.2020.597429

Abstract

Matrine, an active component of Sophora flavescens Ait root extracts, has been used in China for years to treat cancer and viral hepatitis. In the present study, we explored the effects of matrine on hyperglycemia-treated cardiomyocytes. Cardiomyocyte function, oxidative stress, cellular viability, and mitochondrial fusion were assessed through immunofluorescence, quantitative real-time PCR (qRT-PCR), enzyme-linked immunosorbent assays, and RNA interference. Matrine treatment suppressed hyperglycemia-induced oxidative stress in cardiomyocytes by upregulating transcription of nuclear factor erythroid 2-like 2 and heme oxygenase-1. Matrine also improved cardiomyocyte contractile and relaxation function during hyperglycemia, and it reduced hyperglycemia-induced cardiomyocyte death by inhibiting mitochondrial apoptosis. Matrine treatment increased the transcription of mitochondrial fusion-related genes and thus attenuated the proportion of fragmented mitochondria in cardiomyocytes. Inhibiting mitochondrial fusion by knocking down mitofusin 2 (Mfn2) abolished the cardioprotective effects of matrine during hyperglycemia. These results demonstrate that matrine could be an effective drug to alleviate hyperglycemia-induced cardiomyocyte damage by activating Mfn2-induced mitochondrial fusion.

Highlights

The incidence and mortality of diabetic cardiomyopathy are still high in most countries (Makrecka-Kuka et al, 2020)
Hyperglycemia treatment increased mitochondrial reactive oxygen species (ROS) levels, while matrine reduced them (Figures 1C,D). These results indicated that matrine attenuated hyperglycemia-induced oxidative stress in cardiomyocytes
There is a great need to develop new anti-diabetic treatments and modify the existing therapeutic approaches (Sowton et al, 2019) in order to attenuate the complications of diabetes, especially microvascular complications, macrovascular complications, and the diminished quality of life (Heusch, 2018; Karwi et al, 2018)

Summary

Introduction

The incidence and mortality of diabetic cardiomyopathy are still high in most countries (Makrecka-Kuka et al, 2020). In diabetic cardiomyopathy, the equilibrium between mitochondrial fission and fusion is disturbed and shifted toward mitochondrial fission. This mitochondrial phenotype has been found to precede the onset of cardiac functional and structural changes in experimental models, suggesting that abnormal mitochondrial fusion directly promotes the development of diabetic cardiomyopathy (Zhou et al, 2018c,d; Lee et al, 2019). Recent studies have demonstrated that mitochondrial fission contributes to the pathology of hyperglycemia-induced cardiac damage (Zhou et al, 2018c; Hu et al, 2019b). The influence of mitochondrial fusion on the course of diabetic cardiomyopathy has not yet been described

Methods

Results

Conclusion