Regulation of Sirtuin-Mediated Protein Deacetylation by Cardioprotective Phytochemicals.

Niria Treviño-Saldaña,Gerardo García-Rivas

doi:10.1155/2017/1750306

Abstract

Modulation of posttranslational modifications (PTMs), such as protein acetylation, is considered a novel therapeutic strategy to combat the development and progression of cardiovascular diseases. Protein hyperacetylation is associated with the development of numerous cardiovascular diseases, including atherosclerosis, hypertension, cardiac hypertrophy, and heart failure. In addition, decreased expression and activity of the deacetylases Sirt1, Sirt3, and Sirt6 have been linked to the development and progression of cardiac dysfunction. Several phytochemicals exert cardioprotective effects by regulating protein acetylation levels. These effects are mainly exerted via activation of Sirt1 and Sirt3 and inhibition of acetyltransferases. Numerous studies support a cardioprotective role for sirtuin activators (e.g., resveratrol), as well as other emerging modulators of protein acetylation, including curcumin, honokiol, oroxilyn A, quercetin, epigallocatechin-3-gallate, bakuchiol, tyrosol, and berberine. Studies also point to a cardioprotective role for various nonaromatic molecules, such as docosahexaenoic acid, alpha-lipoic acid, sulforaphane, and caffeic acid ethanolamide. Here, we review the vast evidence from the bench to the clinical setting for the potential cardioprotective roles of various phytochemicals in the modulation of sirtuin-mediated deacetylation.

Highlights

Cardiovascular diseases (CVDs) have remained the leading cause of death worldwide for the past two decades
Research on the impact of protein acetylation in CVDs has focused mainly on Sirt1, Sirt3, and Sirt6, with little information regarding the function of the remaining sirtuins
Sirt6−/− deficiency is associated with overexpression of proinflammatory cytokines, such as tumour necrosis factor superfamily member 4 and vascular cell adhesion molecule 1. These findings suggest that maintaining Sirt6 expression might be a novel therapeutic strategy against both cardiac and vascular dysfunction

Summary

Introduction

Cardiovascular diseases (CVDs) have remained the leading cause of death worldwide for the past two decades. Hypertension, peripheral vascular disease, myocardial infarctions, strokes, and heart failure are the most prevalent CVDs [2] Their aetiology is diverse and includes various risk factors, such as aging, obesity, smoking, and diabetes [1]. Among PTMs, most research far has focused on protein phosphorylation, protein acetylation has emerged as a key regulatory mechanism and an attractive therapeutic target in the field of chronic diseases Sirtuins are widely distributed in prokaryotic and eukaryotic species, with seven isoforms characterized in humans [18, 19] They share a common catalytic domain but differ with regard to their N- and C-terminal sequences, which determine their susceptibility to regulation by sirtuinactivating compounds [20] and PTMs (reviewed in [21]). All sirtuins are classified as deacetylases, Sirt and Sirt have weak deacetylase activity and function as demalonylases and deacylases [22, 23] (Figure 1)

Protein Acetylation and CVDs

Bioavailability of Cardioprotective

Potential Toxicity of Phytochemicals

Findings

Conclusion