Abstract
SIRT1 is an NAD+-dependent class III histone deacetylase that is abundantly expressed in the kidney, where it modulates gene expression, apoptosis, energy homeostasis, autophagy, acute stress responses, and mitochondrial biogenesis. Alterations in SIRT1 activity and NAD+ metabolism are frequently observed in acute and chronic kidney diseases of diverse origins, including obesity and diabetes. Nevertheless, in vitro and in vivo studies and clinical trials with humans show that the SIRT1-activating compounds derived from natural sources, such as polyphenols found in fruits, vegetables, and plants, including resveratrol, quercetin, and isoflavones, can prevent disease and be part of treatments for a wide variety of diseases. Here, we summarize the roles of SIRT1 and NAD+ metabolism in renal pathophysiology and provide an overview of polyphenols that have the potential to restore SIRT1 and NAD+ metabolism in renal diseases.
Highlights
Sirtuins constitute a family of nicotinamide adenine dinucleotide (NAD+)-dependent deacetylases that have been conserved during evolution from archaea to mammals; their activity is regulated by metabolic and environmental stimuli [1]
We review the protective effects of sirtuin 1 (SIRT1) and NAD+ metabolism on renal function because these effects have been recently described based on several models of renal disorders with metabolic impairment
MiR-34a and miR-155–5p reduced the expression of SIRT1 [93,94,95]. These results suggested that the downregulation of SIRT1 is mediated through a posttranscriptional mechanism mediated by miRNAs (Figure 2)
Summary
Sirtuins constitute a family of nicotinamide adenine dinucleotide (NAD+)-dependent deacetylases that have been conserved during evolution from archaea to mammals; their activity is regulated by metabolic and environmental stimuli [1]. SIRT1 exerts a protective effect in the kidney by reducing inflammation, oxidative stress, blood pressure, and diabetic albuminuria and by delaying fibrogenesis and renal aging These beneficial effects of SIRT1 in the kidney have been described by several authors [8,27,28] and are due to the deacetylation of specific lysine residues in several signaling network agents and transcription factors, including, among others, nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB); signal transducer and activator of transcription protein (STAT); forkhead box transcription factors (FOXOs); p38 mitogen-activated protein kinases (p38 MAPK); tumor protein p53 (p53); 5’-adenosine monophosphate-activated protein kinase (AMPK); mechanistic target of rapamycin (mTOR); and peroxisome proliferator-activated receptor-gamma coactivator 1 alpha (PGC1α). Levels, improving mitochondrial and kidney function (Figure 2) [73]
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