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NAD AND resveratrol AND sirtuin

Ivan Orlandi, Giulia Stamerra, Maurizio Strippoli, Marina Vai
Resveratrol (RSV) is a naturally occurring polyphenolic compound endowed with interesting biological properties/functions amongst which are its activity as an antioxidant and as Sirtuin activating compound towards SIRT1 in mammals. Sirtuins comprise a family of NAD(+)-dependent protein deacetylases that are involved in many physiological and pathological processes including aging and age-related diseases. These enzymes are conserved across species and SIRT1 is the closest mammalian orthologue of Sir2 of Saccharomyces cerevisiae...
April 9, 2017: Redox Biology
Yasunari Kayashima, Yuki Katayanagi, Keiko Tanaka, Ryuta Fukutomi, Shigeru Hiramoto, Shinjiro Imai
Sirtuins are enzymes that catalyze NAD+ dependent protein deacetylation. The natural polyphenolic compound resveratrol received renewed interest when recent findings implicated resveratrol as a potent SIRT1 activator capable of mimicking the effects of calorie restriction. However, resveratrol directly interacts with fluorophore-containing peptide substrates. It was demonstrated that the SIRT1 activation of resveratrol is affected by the amino acid composition of the substrate. Resveratrol did increase the enzyme activity in cases in which hydrophobic amino acids are at the +1 position to the acetylated lysine in the substrate...
March 2, 2017: Scientific Reports
Jian-Jun Deng, Ka-Yiu Edwin Kong, Wei-Wei Gao, Hei-Man Vincent Tang, Vidyanath Chaudhary, Yun Cheng, Jie Zhou, Chi-Ping Chan, Danny Ka-Ho Wong, Man-Fung Yuen, Dong-Yan Jin
Hepatitis B virus (HBV) genome is organized into a minichromosome known as covalently closed circular DNA (cccDNA), which serves as the template for all viral transcripts. SIRT1 is an NAD(+)-dependent protein deacetylase which activates HBV transcription by promoting the activity of cellular transcription factors and coactivators. How SIRT1 and viral transactivator X protein (HBx) might affect each other remains to be clarified. In this study we show synergy and mutual dependence between SIRT1 and HBx in the activation of HBV transcription...
February 24, 2017: Biochimica et Biophysica Acta
Wei-Rong Wang, Ting-Ting Li, Ting Jing, Yan-Xiang Li, Xiao-Feng Yang, Yan-Hao He, Wei Zhang, Rong Lin, Ji-Ye Zhang
BACKGROUND/AIMS: Autophagy is a lysosomal degradation pathway that is essential for cellular survival, differentiation, and homeostasis. Sirtuin 1 (SIRT1), a NAD+-dependent deacetylase, plays a pivotal role in modulation of autophagy. Recent studies found that autophagy was involved in the regulation of inflammatory response. In this study, we aimed to determine the effect of SIRT1 on autophagy and inflammation, and whether autophagy can regulate the inflammatory response in vascular adventitial fibroblasts (VAFs)...
February 3, 2017: Cellular Physiology and Biochemistry
Luana Naia, Tatiana R Rosenstock, Ana M Oliveira, Sofia I Oliveira-Sousa, Gladys L Caldeira, Catarina Carmo, Mário N Laço, Michael R Hayden, Catarina R Oliveira, A Cristina Rego
Sirtuin 1 (SIRT1) is a nicotinamide adenine dinucleotide (NAD(+))-dependent lysine deacetylase that regulates longevity and enhances mitochondrial metabolism. Both activation and inhibition of SIRT1 were previously shown to ameliorate neuropathological mechanisms in Huntington's disease (HD), a neurodegenerative disease that selectively affects the striatum and cortex and is commonly linked to mitochondrial dysfunction. Thus, in this study, we tested the influence of resveratrol (RESV, a SIRT1 activator) versus nicotinamide (NAM, a SIRT1 inhibitor) in counteracting mitochondrial dysfunction in HD models, namely striatal and cortical neurons isolated from YAC128 transgenic mice embryos, HD human lymphoblasts, and an in vivo HD model...
September 2, 2016: Molecular Neurobiology
Michael S Bonkowski, David A Sinclair
The sirtuins (SIRT1-7) are a family of nicotinamide adenine dinucleotide (NAD(+))-dependent deacylases with remarkable abilities to prevent diseases and even reverse aspects of ageing. Mice engineered to express additional copies of SIRT1 or SIRT6, or treated with sirtuin-activating compounds (STACs) such as resveratrol and SRT2104 or with NAD(+) precursors, have improved organ function, physical endurance, disease resistance and longevity. Trials in non-human primates and in humans have indicated that STACs may be safe and effective in treating inflammatory and metabolic disorders, among others...
November 2016: Nature Reviews. Molecular Cell Biology
Jessica L Fry, Leona Al Sayah, Robert M Weisbrod, Isabelle Van Roy, Xiang Weng, Richard A Cohen, Markus M Bachschmid, Francesca Seta
Arterial stiffness, a major cardiovascular risk factor, develops within 2 months in mice fed a high-fat, high-sucrose (HFHS) diet, serving as a model of human metabolic syndrome, and it is associated with activation of proinflammatory and oxidant pathways in vascular smooth muscle (VSM) cells. Sirtuin-1 (SirT1) is an NAD(+)-dependent deacetylase regulated by the cellular metabolic status. Our goal was to study the effects of VSM SirT1 on arterial stiffness in the context of diet-induced metabolic syndrome. Overnight fasting acutely decreased arterial stiffness, measured in vivo by pulse wave velocity, in mice fed HFHS for 2 or 8 months, but not in mice lacking SirT1 in VSM (SMKO)...
September 2016: Hypertension
Jeannette C Bleeker, Riekelt H Houtkooper
Protein acylation has emerged as a large family of post translational modifications in which an acyl group can alter the function of a wide variety of proteins, especially in response to metabolic stress. The acylation state is regulated through reversible acylation/deacylation. Acylation occurs enzymatically or non-enzymatically, and responds to acyl-CoA levels. Deacylation on the other hand is controlled through the NAD(+)-dependent sirtuin proteins. In several inborn errors of metabolism (IEMs), accumulation of acyl-CoAs, due to defects in amino acid and fatty acid metabolic pathways, can lead to hyperacylation of proteins...
July 2016: Journal of Inherited Metabolic Disease
Xiao-Dong Zou, Shao-Qing Guo, Zhi-Wei Hu, Wei-Lang Li
Parkinson's disease (PD) is the second most common progressive neurodegenerative movement disorder. Nicotinamide phosphoribosyltransferase (NAMPT) catalyzes the first rate‑limiting step in the nicotinamide adenine dinucleotide (NAD+) biosynthetic pathway in mammals, is a substrate for NAD+‑dependent enzymes, such as sirtuin 1 (SIRT1), and contributes to cell fate decisions. However, the role of NAMPT in PD has remained to be fully elucidated. In the present study, PC12 cells were treated with the neurotoxin 6-hydroxydopamine (6‑OHDA) to establish an in vitro model of PD, following which an obvious inhibitory effect on the levels of NAMPT and NAD+ as well as the NAD+/NADH ratio was detected...
May 2016: Molecular Medicine Reports
Ying Hui Li, Dae Hee Choi, Eun Hye Lee, Su Ryeon Seo, Seungkoo Lee, Eun-Hee Cho
Sirtuin 3 (SIRT3) is an NAD(+)-dependent protein deacetylase. Recent studies have shown that SIRT3 expression is decreased in nonalcoholic fatty liver disease (NAFLD). Moreover, SIRT3 is a key regulator of succinate dehydrogenase (SDH), which catalyzes the oxidation of succinate to fumarate. Increased succinate concentrations and the specific G protein-coupled receptor 91 (GPR91) are involved in the activation of hepatic stellate cells (HSCs). In this study, we aimed to establish whether SIRT3 regulated the SDH activity, succinate, and GPR91 expression in HSCs and an animal model of NAFLD...
May 6, 2016: Journal of Biological Chemistry
Liqun Ma, Rongguo Fu, Zhaoyang Duan, Jiamei Lu, Jie Gao, Lifang Tian, Zhian Lv, Zhao Chen, Jin Han, Lining Jia, Li Wang
Type 2 diabetic nephropathy (DN) is a serious end-stage kidney disease worldwide. Multiple studies demonstrate that resveratrol (RSV) has a beneficial effect on DN. However, whether RSV-induced improvement in kidney function in diabetes is due to the regulation of autophagy remains unclear. Here, we investigated the mechanisms underlying RSV-mediated protection against DN in diabetic rats, with a special focus on the role of NAD-dependent deacetylase sirtuin 1 (Sirt1) in regulating autophagy. We found that long-term RSV treatment in rats promoted Sirt1 expression and improved related metabolic levels in the diabetic kidney...
April 2016: Pathology, Research and Practice
Nady Braidy, Bat-Erdene Jugder, Anne Poljak, Tharusha Jayasena, Hussein Mansour, Seyed Mohammad Nabavi, Perminder Sachdev, Ross Grant
Resveratrol (3,4',5-trihydroxystilbene) is a naturally occurring phytochemical present in red wine, grapes, berries, chocolate and peanuts. Clinically, resveratrol has exhibited significant antioxidant, anti-inflammatory, anti-viral, and anti-cancer properties. Although resveratrol was first isolated in 1940, it was not until the last decade that it was recognised for its potential therapeutic role in reducing the risk of neurodegeneration, and Alzheimer's disease (AD) in particular. AD is the primary cause of progressive dementia...
2016: Current Topics in Medicinal Chemistry
Juan Gui, Arne Potthast, Anne Rohrbach, Katja Borns, Anibh M Das, Frauke von Versen-Höynck
BACKGROUND: Gestational diabetes (GDM) has long-term consequences for the offspring. Sirtuins (SIRTs) are associated with vascular and metabolic functions. We studied the impact of GDM on SIRT activity and expression in fetal endothelial colony-forming cells (ECFCs) and human umbilical vein endothelial cells (HUVECs) from pregnancies complicated by GDM. METHODS: ECFCs and HUVECs were isolated from cord and cord blood of 10 uncomplicated pregnancies (NPs) and 10 GDM pregnancies...
May 2016: Pediatric Research
Ana Elena Peredo-Escárcega, Verónica Guarner-Lans, Israel Pérez-Torres, Sergio Ortega-Ocampo, Elizabeth Carreón-Torres, Vicente Castrejón-Tellez, Eulises Díaz-Díaz, María Esther Rubio-Ruiz
Resveratrol (RSV) and quercetin (QRC) modify energy metabolism and reduce cardiovascular risk factors included in the metabolic syndrome (MetS). These natural compounds upregulate and activate sirtuins (SIRTs), a family of NAD-dependent histone deacetylases. We analyzed the effect of two doses of a commercial combination of RSV and QRC on serum fatty acid composition and their regulation of SIRTs 1-3 and PPAR-γ expression in white adipose tissue. MetS was induced in Wistar rats by adding 30% sucrose to drinking water for five months...
2015: Evidence-based Complementary and Alternative Medicine: ECAM
Tao Yang, Shugang Li, Xuming Zhang, Xiaowu Pang, Qinlu Lin, Jianzhong Cao
Resveratrol is a natural phenolic product found in some plants in response to stress and has been linked to the many health benefits of red wine. Over the past several decades, a great deal of research has identified diverse biological roles associated with resveratrol, including anti-oxidant, anti-proliferation, anti-inflammation, anti-cancer, anti-fungal, and antiviral activities. Such biological activities of resveratrol are likely mediated through multiple cellular targets or pathways, such as sirtuins, a family of NAD(+)-dependent deacetylases...
November 2015: Reviews in Medical Virology
Y Ghinis-Hozumi, L González-Dávalos, A Antaramian, F Villarroya, E Piña, A Shimada, A Varela-Echavarría, O Mora
Sirtuins (Sirt) are NAD-dependent deacetylases that are activated by the antioxidants resveratrol (RSV) and lipoic acid (LA). The objective of this study was to determine in bovine liver and muscle slice cultures the effect of RSV and LA treatment on the expresssion of Sirt1, Sirt3, peroxisome proliferator-activated receptor γ coactivator 1α (PPARGC1A), and the forkhead box O transcription factors FoxO1 and FoxO3 as well as other factors involved in glucose and lipid metabolism and related to Sirt activity...
August 2015: Journal of Animal Science
Duanfang Cao, Mingzhu Wang, Xiayang Qiu, Dongxiang Liu, Hualiang Jiang, Na Yang, Rui-Ming Xu
Sirtuins with an extended N-terminal domain (NTD), represented by yeast Sir2 and human SIRT1, harbor intrinsic mechanisms for regulation of their NAD-dependent deacetylase activities. Elucidation of the regulatory mechanisms is crucial for understanding the biological functions of sirtuins and development of potential therapeutics. In particular, SIRT1 has emerged as an attractive therapeutic target, and the search for SIRT1-activating compounds (STACs) has been actively pursued. However, the effectiveness of a class of reported STACs (represented by resveratrol) as direct SIRT1 activators is under debate due to the complication involving the use of fluorogenic substrates in in vitro assays...
June 15, 2015: Genes & Development
Rong Guo, Weijing Liu, Baoxin Liu, Buchun Zhang, Weiming Li, Yawei Xu
BACKGROUND: Endoplasmic reticulum (ER) stress-dependent apoptosis had been shown to occur in the hearts of people with diabetes, although the exact mechanisms are unclear. Sirtuin 1 (SIRT1), a nicotinamide adenine dinucleotide NAD(+)-dependent deacetylase, is known to play a role in diabetes-related complications as well as ER-stress. Therefore, we investigated the relationship between Sirtuin 1 (SIRT1) and ER stress-induced apoptosis in H9C2 cardiomyocyte. METHODS: Diabetic rats were established by a single intraperitoneal injection of streptozotocin (STZ; 50mg/kg) with high-fat diet...
July 15, 2015: International Journal of Cardiology
Mehtap Kilic Eren, Ayten Kilincli, Özkan Eren
The natural polyphenolic compound resveratrol (3,4,5-trihydroxy-trans-stilbene) has broad spectrum health beneficial activities including antioxidant, anti-inflammatory, anti-aging, anti-cancer, cardioprotective, and neuroprotective effects. Remarkably, resveratrol also induces apoptosis and cellular senescence in primary and cancer cells. Resveratrol's anti-aging effects both in vitro and in vivo attributed to activation of a (NAD)-dependent histone deacetylase family member sirtuin-1 (SIRT1) protein. In mammals seven members (SIRT1-7) of sirtuin family have been identified...
2015: PloS One
Lane M Smith, Jonathan D Wells, Vidula T Vachharajani, Barbara K Yoza, Charles E McCall, J Jason Hoth
BACKGROUND: Pulmonary contusion (PC) is a common, potentially lethal injury that results in priming for exaggerated inflammatory responses to subsequent immune challenge like infection (second hit). The molecular mechanism of priming and the second hit phenomenon after PC remain obscure. With the use of a mouse model of PC, this study explores the role of sirtuin 1 (SIRT1), an NAD+-dependent deacetylase, in priming for a second hit after injury. METHODS: With the use of a mouse model of PC, injury-primed second-hit host responses were tested at 24 hours after PC by (1) in vivo infectious challenge of injured mice or (2) ex vivo inflammatory challenge of isolated immune cells from injured mice...
May 2015: Journal of Trauma and Acute Care Surgery
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