Cellular and molecular effects of resveratrol in health and disease

Yu, Wei; Fu, Yucai; Wang, Wei

doi:10.1002/jcb.23431

Cited by 162 publications

(109 citation statements)

References 97 publications

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“…In our study also, the combined use of resveratrol with leptin modifi es the tissue injury by leptin-induced STAT3 phosphorylation. Caspase 3 is a key enzyme that leads to apoptosis in various cell types (23). According to control group, although there was a small increase in caspase 3 protein expression in sham group, but this elevation was not signifi cant.…”

Section: Discussionmentioning

confidence: 93%

The effect of leptin and resveratrol on JAK/STAT pathways and Sirt-1 gene expression in the renal tissue of ischemia/reperfusion induced rats

Erkasap¹,

Erkasap²,

Bradford³

et al. 2017

BLL

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OBJECTIVE: Our study aimed to investigate the possible modifying effects of leptin and combined use of resveratrol on rat renal I/R injury and their relationship on signal pathways and apoptosis-related mechanisms. BACKGROUND: Renal ischemia-reperfusion (I/R) injury is an important cause of acute renal failure. METHODS: Male Sprague Dawley rats were divided into 5 groups: Control, I/R, I/R+leptin, I/R+resveratrol and I/R+leptin+resveratrol. Leptin (10 μg/kg BW) was administered (i.p.) 30 min prior to I/R. Resveratrol was administered by gavage at 20 mg/kg BW per d for 12 d prior to I/R. The left renal artery was exposed to 1 h of ischemia and 1 h of reperfusion. RESULTS: Resveratrol treatment alone increased TNF-α, TNF-α R1, NF-κB, SIRT-1, STAT1 and STAT3 mRNA levels and decreased caspase 3 protein levels. Leptin treatment alone signifi cantly decreased the caspase 3 protein levels. The combined use of resveratrol and leptin signifi cantly increased STAT3, and caspase 3 mRNA levels, and decreased the caspase 3 protein levels. Apoptosis was signifi cantly decreased especially in the leptin and leptin+resveratrol groups. CONCLUSION: The present study suggest that a combined use of resveratrol and leptin has preventive and regulatory effects on renal I/R injury; the mechanism involves decreasing apoptosis, likely by altering the JAK/ STAT pathway and SIRT1 expression (Fig. 8, Ref. 24). Text in PDF www.elis.sk.

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Section: Discussionmentioning

confidence: 93%

The effect of leptin and resveratrol on JAK/STAT pathways and Sirt-1 gene expression in the renal tissue of ischemia/reperfusion induced rats

Erkasap¹,

Erkasap²,

Bradford³

et al. 2017

BLL

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“…MS-275 has demonstrated anti-tumor activity and is currently under evaluation in phase II clinical trials for cancer therapy (Tan et al, 2010). Resveratrol is a widely studied polyphenol endowed with antiaging, anti-carcinogenic, anti-inflammatory and anti-oxidant properties (reviewed in Yu et al, 2012). It is also under clinical evaluation for the treatment of cancer, metabolic disorders, cardiovascular diseases and cognitive dysfunction in old patients (Smoliga et al, 2011).…”

Section: Introductionmentioning

confidence: 99%

Targeted acetylation of NF-kappaB/RelA and histones by epigenetic drugs reduces post-ischemic brain injury in mice with an extended therapeutic window

Lanzillotta

Pignataro²,

Branca

et al. 2013

Neurobiology of Disease

110

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Nuclear factor-kappaB (NF-κB) p50/RelA is a key molecule with a dual effect in the progression of ischemic stroke. In harmful ischemia, but not in preconditioning insult, neurotoxic activation of p50/RelA is characterized by RelA-specific acetylation at Lys310 (K310) and deacetylation at other Lys residues. The derangement of RelA acetylation is associated with activation of Bim promoter. Objective: With the aim of producing neuroprotection by correcting altered acetylation of RelA in brain ischemia, we combined the pharmacological inhibition of histone deacetylase (HDAC) 1-3, the enzymes known to reduce global RelA acetylation, and the activation of sirtuin 1, endowed with a specific deacetylase activity on the K310 residue of RelA. To afford this aim, we tested the clinically used HDAC 1-3 inhibitor entinostat (MS-275) and the sirtuin 1 activator resveratrol. Methods: We used the mouse model of transient middle cerebral artery occlusion (MCAO) and primary cortical neurons exposed to oxygen glucose deprivation (OGD). Results: The combined use of MS-275 and resveratrol, by restoring normal RelA acetylation, elicited a synergistic neuroprotection in neurons exposed to OGD. This effect correlated with MS-275 capability to increase total RelA acetylation and resveratrol capability to reduce RelA K310 acetylation through the activation of an AMPactivated protein kinase-sirtuin 1 pathway. The synergistic treatment reproduced the acetylation state of RelA peculiar of preconditioning ischemia. Neurons exposed to the combined drugs totally recovered the optimal histone H3 acetylation. Neuroprotection was reproduced in mice subjected to MCAO and treated with MS-275 (20 μg/kg and 200 μg/kg) or resveratrol (6800 μg/kg) individually. However, the administration of lowest doses of MS-275 (2 μg/kg) and resveratrol (68 μg/kg) synergistically reduced infarct volume and neurological deficits. Importantly, the treatment was effective even when administered 7 h after the stroke onset. Chromatin immunoprecipitation analysis of cortices harvested from treated mice showed that the RelA binding and histone acetylation increased at the Bcl-x L promoter and decreased at the Bim promoter. Conclusion: Our study reveals that epigenetic therapy shaping acetylation of both RelA and histones may be a promising strategy to limit post-ischemic injury with an extended therapeutic window.

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“…One stilbene derivative of note is resveratrol, which is a plant phytoalexin abundant in grapes and peanuts. Studies have demonstrated numerous health benefits related to the consumption of resveratrol, which is correlated with reduced cardiovascular disease and cancer (1). Lignostilbene α,β-dioxygenase (LSD, EC 1.13.11.43), originally observed in Sphingomonas paucimobilis, was the first enzyme shown to cleave the central double bond of stilbenes, forming two phenolic aldehydes (2,3).…”

mentioning

confidence: 99%

Structure and mechanism of NOV1, a resveratrol-cleaving dioxygenase

McAndrew

Sathitsuksanoh

Mbughuni

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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Stilbenes are diphenyl ethene compounds produced naturally in a wide variety of plant species and some bacteria. Stilbenes are also derived from lignin during kraft pulping. Stilbene cleavage oxygenases (SCOs) cleave the central double bond of stilbenes, forming two phenolic aldehydes. Here, we report the structure of an SCO. The X-ray structure of NOV1 from Novosphingobium aromaticivorans was determined in complex with its substrate resveratrol (1.89 Å), its product vanillin (1.75 Å), and without any bound ligand (1.61 Å). The enzyme is a seven-bladed β-propeller with an iron cofactor coordinated by four histidines. In all three structures, dioxygen is observed bound to the iron in a side-on fashion. These structures, along with EPR analysis, allow us to propose a mechanism in which a ferric-superoxide reacts with substrate activated by deprotonation of a phenol group at position 4 of the substrate, which allows movement of electron density toward the central double bond and thus facilitates reaction with the ferric superoxide electrophile. Correspondingly, NOV1 cleaves a wide range of other stilbene-like compounds with a 4′-OH group, offering potential in processing some solubilized fragments of lignin into monomer aromatic compounds.tilbenes are diphenyl ethene compounds that are produced naturally in a wide variety of plant species and some bacteria. One stilbene derivative of note is resveratrol, which is a plant phytoalexin abundant in grapes and peanuts. Studies have demonstrated numerous health benefits related to the consumption of resveratrol, which is correlated with reduced cardiovascular disease and cancer (1). Lignostilbene α,β-dioxygenase (LSD, EC 1.13.11.43), originally observed in Sphingomonas paucimobilis, was the first enzyme shown to cleave the central double bond of stilbenes, forming two phenolic aldehydes (2, 3). Subsequently, NOV1 and NOV2 (4) from Novosphingobium aromaticivorans, Rco1 (5) from Ustilago maydis, and CAO-1 (6) from Neurospora crassa were also shown to be stilbene cleaving oxygenases (SCOs). SCOs are related to carotenoid cleavage oxygenases (CCOs), which are enzymes that oxidatively cleave β-carotene or apocarotenoids. Carotenoids are a diverse class of molecules that play important roles in photosynthesis, immune function, and light perception in the eye. CCOs have been studied in great detail, including several crystal structures (7-9).Here, we present the X-ray structure of an SCO, NOV1 from N. aromaticivorans (NOV1). The structure was determined in complex with a representative substrate (resveratrol), a representative product (vanillin), and without ligand bound. We have also observed the ternary complex with oxygen and substrate or product bound, which has not been previously detected in a crystal structure of any CCO-related enzyme. Despite being related to CCOs, this structure of NOV1 shows several key differences that are indicative of their disparate substrate specificities. Moreover, the observed placement of Fe, O 2 , and the phenolic substrate resveratrol in th...

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Cellular and molecular effects of resveratrol in health and disease

Cited by 162 publications

References 97 publications

The effect of leptin and resveratrol on JAK/STAT pathways and Sirt-1 gene expression in the renal tissue of ischemia/reperfusion induced rats

The effect of leptin and resveratrol on JAK/STAT pathways and Sirt-1 gene expression in the renal tissue of ischemia/reperfusion induced rats

Targeted acetylation of NF-kappaB/RelA and histones by epigenetic drugs reduces post-ischemic brain injury in mice with an extended therapeutic window

Structure and mechanism of NOV1, a resveratrol-cleaving dioxygenase

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