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线粒体:多酚类物质治疗糖尿病心肌病的作用靶点。

The Mitochondria: A Target of Polyphenols in the Treatment of Diabetic Cardiomyopathy.

机构信息

Department of Pharmacology and Toxicology, American University of Beirut, Beirut 11-0236, Lebanon.

Department of Pharmacology and Therapeutics, Beirut Arab University, Beirut 11-5020, Lebanon.

出版信息

Int J Mol Sci. 2020 Jul 14;21(14):4962. doi: 10.3390/ijms21144962.

Abstract

Diabetic cardiomyopathy (DCM) is a constellation of symptoms consisting of ventricular dysfunction and cardiomyocyte disarray in the presence of diabetes. The exact cause of this type of cardiomyopathy is still unknown; however, several processes involving the mitochondria, such as lipid and glucose metabolism, reactive oxygen species (ROS) production, apoptosis, autophagy and mitochondrial biogenesis have been implicated. In addition, polyphenols have been shown to improve the progression of diabetes. In this review, we discuss some of the mechanisms by which polyphenols, particularly resveratrol, play a role in slowing the progression of DCM. The most important intermediates by which polyphenols exert their protective effect include Bcl-2, UCP2, SIRT-1, AMPK and JNK1. Bcl-2 acts to attenuate apoptosis, UCP2 decreases oxidative stress, SIRT-1 increases mitochondrial biogenesis and decreases oxidative stress, AMPK increases autophagy, and JNK1 decreases apoptosis and increases autophagy. Our dissection of these molecular players aims to provide potential therapeutic targets for the treatment of DCM.

摘要

糖尿病心肌病(DCM)是一组在糖尿病存在的情况下出现心室功能障碍和心肌细胞排列紊乱的症状。这种心肌病的确切原因尚不清楚;然而,涉及线粒体的几个过程,如脂质和葡萄糖代谢、活性氧(ROS)产生、细胞凋亡、自噬和线粒体生物发生,已经被牵连进来。此外,多酚已被证明可以改善糖尿病的进展。在这篇综述中,我们讨论了多酚,特别是白藜芦醇,在减缓 DCM 进展中发挥作用的一些机制。多酚发挥其保护作用的最重要的中间产物包括 Bcl-2、UCP2、SIRT-1、AMPK 和 JNK1。Bcl-2 可以减轻细胞凋亡,UCP2 减少氧化应激,SIRT-1 增加线粒体生物发生并减少氧化应激,AMPK 增加自噬,而 JNK1 减少细胞凋亡并增加自噬。我们对这些分子参与者的剖析旨在为 DCM 的治疗提供潜在的治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f0f9/7404043/42c96fbb24bf/ijms-21-04962-g002.jpg

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