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Sirt3 AND Resveratrol

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https://www.readbyqxmd.com/read/27611176/autophagy-and-mitochondrial-dysfunction-in-adjuvant-arthritis-rats-treatment-with-resveratrol
#1
Junqiang Zhang, Xianbin Song, Wei Cao, Jinseng Lu, Xiaoqing Wang, Gaoyuan Wang, Zhicheng Wang, Xiaoyu Chen
Resveratrol is a polyphenol derivatives which exhibits a pro-apoptotic effect in a variety of human cancers by triggering mitochondria apoptosis pathway and autophagy. However, there are scarcely reports on its apoptosis-promoting effect in abnormal proliferation fibroblast-like synoviocytes (FLSs). In this study, we investigated the underlying mechanism and apoptosis-inducing effects of resveratrol on the abnormal proliferation of FLSs in adjuvant-arthritis (AA) rats. Since using resveratrol for 12 days resulted in a significant decreasing the swelling degree of the paw, reducing malondialdehyde (MDA) content and enhancing superoxide dismutase (SOD) activity, antioxidant capacity, glutathione peroxidase and glutathione reductase ratio in AA rats...
September 9, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27522058/sirtuin-3-deregulation-promotes-pulmonary-fibrosis
#2
Meredith L Sosulski, Rafael Gongora, Carol Feghali-Bostwick, Joseph A Lasky, Cecilia G Sanchez
Oxidative stress leads to alveolar epithelial cell injury and fibroblast-myofibroblast differentiation (FMD), key events in the pathobiology of pulmonary fibrosis (PF). Sirtuin 3 (SIRT3) is a mitochondrial protein deacetylase regulator of antioxidant response and mitochondrial homeostasis. Here, we demonstrate reduced SIRT3 expression in the lungs of old mice compared to young mice, as well as in two murine models of PF. The analysis of the pattern of SIRT3 expression in the lungs of patients with PF revealed low SIRT3 staining within the fibrotic regions...
August 13, 2016: Journals of Gerontology. Series A, Biological Sciences and Medical Sciences
https://www.readbyqxmd.com/read/27126960/resveratrol-attenuates-oxidative-stress-in-mitochondrial-complex-i-deficiency-involvement-of-sirt3
#3
Lise Mathieu, Alexandra Lopes Costa, Carole Le Bachelier, Abdelhamid Slama, Anne-Sophie Lebre, Robert W Taylor, Jean Bastin, Fatima Djouadi
The pathophysiological mechanisms underlying Complex I (CI) deficiencies are understood only partially which severely limits the treatment of this common, devastating, mitochondrial disorder. Recently, we have shown that resveratrol (RSV), a natural polyphenol, has beneficial effects on CI deficiency of nuclear origin. Here, we demonstrate that RSV is able to correct the biochemical defect in oxygen consumption in five of thirteen CI-deficient patient cell lines. Other beneficial effects of RSV include a decrease of total intracellular ROS and the up-regulation of the expression of mitochondrial superoxide dismutase (SOD2) protein, a key antioxidant defense enzyme...
July 2016: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/27067422/polydatin-ameliorates-injury-to-the-small-intestine-induced-by-hemorrhagic-shock-via-sirt3-activation-mediated-mitochondrial-protection
#4
Zhenhua Zeng, Yating Yang, Xingui Dai, Siqi Xu, Tao Li, Qin Zhang, Ke-Seng Zhao, Zhongqing Chen
BACKGROUND: Previously, we demonstrated that sirtuin (SIRT)1 plays vital roles in the small intestine (SI), protecting against severe hemorrhagic shock (HS), and that polydatin (PD) can attenuate SI injury via SIRT1 activation. OBJECTIVE: To explore the role of SIRT3 and mitochondria in SI injury after HS, and explore SIRT3 as a therapeutic target of PD in HS. METHODS: An H2O2-induced model of oxidative stress and an HS model were created in IEC-6 cells and Sprague-Dawley rats, respectively...
June 2016: Expert Opinion on Therapeutic Targets
https://www.readbyqxmd.com/read/27064125/activation-of-sirt3-attenuates-triptolide-induced-toxicity-through-closing-mitochondrial-permeability-transition-pore-in-cardiomyocytes
#5
Yanqin Yang, Wenwen Wang, Zhewen Xiong, Jiamin Kong, Yuwen Qiu, Feihai Shen, Zhiying Huang
Triptolide (TP), an active component of the traditional Chinese herb Tripterygium wilfordii Hook f. (TWHF), has multiple pharmacological effects. However, the severe toxicity of TP greatly restricts its clinical applications. Although TP exposure causes serious heart injury, the mechanism underlying TP-induced cardiotoxicity has rarely been investigated. In previous studies, we found that TP-induced oxidative stress was involved in the mitochondria-dependent apoptosis of cardiomyocytes. Opening of the mitochondrial permeability transition pore (mPTP) is the key to the mitochondrial dysfunction in cardiac toxicity...
August 2016: Toxicology in Vitro: An International Journal Published in Association with BIBRA
https://www.readbyqxmd.com/read/27021965/a-sirt3-ampk-autophagy-network-orchestrates-the-protective-effects-of-trans-resveratrol-in-stressed-peritoneal-macrophages-and-raw-264-7-macrophages
#6
Wen-Jun Duan, Yi-Fang Li, Fang-Lan Liu, Jie Deng, Yan-Ping Wu, Wei-Lin Yuan, Bun Tsoi, Jun-Li Chen, Qi Wang, Shao-Hui Cai, Hiroshi Kurihara, Rong-Rong He
Resveratrol gains a great interest for its strong antioxidant properties, while the molecular mechanisms underlie the beneficial effects on psychosocial stress remain controversial. In this study, we demonstrated that resveratrol protected peritoneal macrophages and RAW 264.7 cells from stress-induced decrease in the total cell count, phagocytic capability, reactive oxygen species generation, monodansylcadaverine and mitochondrial membrane potential in stressed mice. Resveratrol promoted stress-induced autophagy in both models...
June 2016: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/26912655/sirtuin-3-sirt3-regulates-%C3%AE-smooth-muscle-actin-%C3%AE-sma-production-through-the-succinate-dehydrogenase-g-protein-coupled-receptor-91-gpr91-pathway-in-hepatic-stellate-cells
#7
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
https://www.readbyqxmd.com/read/26717002/gestational-diabetes-induces-alterations-of-sirtuins-in-fetal-endothelial-cells
#8
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
https://www.readbyqxmd.com/read/26573558/resveratrol-alleviates-the-cytotoxicity-induced-by-the-radiocontrast-agent-ioxitalamate-by-reducing-the-production-of-reactive-oxygen-species-in-hk-2-human-renal-proximal-tubule-epithelial-cells-in-vitro
#9
Yen Ta Huang, Yi Ya Chen, Yu Hsien Lai, Chuan Chu Cheng, Tzu Chun Lin, Ying Shih Su, Chin Hung Liu, Pei Chun Lai
Radiocontrast-induced nephropathy (RIN) is one of the leading causes of hospital-acquired acute kidney injury (AKI). The clinical strategies currently available for the prevention of RIN are insufficient. In this study, we aimed to determine whether resveratrol, a polyphenol phytoalexin, can be used to prevent RIN. For this purpose, in vitro experiments were performed using a human renal proximal tubule epithelial cell line (HK-2 cells). Following treatment for 48 h, the highly toxic radiocontrast agent, ioxitalamate, exerted cytotoxic effects on the HK-2 cells in a concentration-dependent manner, as shown by MTT assay...
January 2016: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/26440162/effect-of-resveratrol-and-lipoic-acid-on-sirtuin-regulated-expression-of-metabolic-genes-in-bovine-liver-and-muscle-slice-cultures
#10
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
https://www.readbyqxmd.com/read/26334640/the-molecular-mechanism-of-amyloid-%C3%AE-42-peptide-toxicity-the-role-of-sphingosine-kinase-1-and-mitochondrial-sirtuins
#11
Magdalena Cieślik, Grzegorz A Czapski, Joanna B Strosznajder
Our study focused on the relationship between amyloid β 1-42 (Aβ), sphingosine kinases (SphKs) and mitochondrial sirtuins in regulating cell fate. SphK1 is a key enzyme involved in maintaining sphingolipid rheostat in the brain. Deregulation of the sphingolipid metabolism may play a crucial role in the pathogenesis of Alzheimer's disease (AD). Mitochondrial function and mitochondrial deacetylases, i.e. sirtuins (Sirt3,-4,-5), are also important for cell viability. In this study, we evaluated the interaction between Aβ1-42, SphKs and Sirts in cell survival/death, and we examined several compounds to indicate possible target(s) for a strategy protecting against cytotoxicity of Aβ1-42...
2015: PloS One
https://www.readbyqxmd.com/read/26095584/the-phytoalexin-resveratrol-ameliorates-ochratoxin-a-toxicity-in-human-embryonic-kidney-hek293-cells
#12
Shanel Raghubeer, Savania Nagiah, Alisa Phulukdaree, Anil Chuturgoon
Ochratoxin A (OTA) is a nephrotoxic mycotoxin produced by Aspergillus and Penicillium fungi. It contaminates human and animal food products, and chronic exposure is associated with renal fibrosis in humans (Balkan endemic nephropathy). Resveratrol, a phytoalexin, possesses anti-cancer and antioxidant properties. We investigated the mechanism of cellular oxidative stress induced by OTA, and the effect of resveratrol in human embryonic kidney (HEK293) cells over 24 and 48 h. Cells were exposed to OTA [IC50 = 1...
December 2015: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/25686565/resveratrol-improves-high-fat-diet-induced-insulin-resistance-by-rebalancing-subsarcolemmal-mitochondrial-oxidation-and-antioxidantion
#13
Zhang Haohao, Qin Guijun, Zheng Juan, Kong Wen, Chen Lulu
Although resveratrol (RES) is thought to be a key regulator of insulin sensitivity in rodents, the exact mechanism underlying this effect remains unclear. Therefore, we sought to investigate how RES affects skeletal muscle oxidative and antioxidant levels of subsarcolemmal (SS) and intermyofibrillar (IMF) mitochondrial populations in high-fat diet (HFD)-induced insulin resistance (IR) rats. Systemic and skeletal muscle insulin sensitivity together with expressions of several genes related to mitochondrial biogenesis and skeletal muscle SIRT1, SIRT3 protein levels were studied in rats fed a normal diet, a HFD, and a HFD with intervention of RES for 8 weeks...
March 2015: Journal of Physiology and Biochemistry
https://www.readbyqxmd.com/read/25527776/activation-of-sirt3-by-resveratrol-ameliorates-cardiac-fibrosis-and-improves-cardiac-function-via-the-tgf-%C3%AE-smad3-pathway
#14
Tongshuai Chen, Jingyuan Li, Junni Liu, Na Li, Shujian Wang, Hui Liu, Mei Zeng, Yun Zhang, Peili Bu
Sirtuins [sirtuin (SIRT)1-SIRT7] mediate the longevity-promoting effects of calorie restriction in yeast, worms, flies, and mice. Additionally, SIRT3 is the only SIRT analog whose increased expression has been shown to be associated with longevity in humans. The polyphenol resveratrol (RSV) is the first compound discovered able to mimic calorie restriction by stimulating SIRTs. In the present study, we report that RSV activated SIRT3 in cardiac fibroblasts both in vivo and in vitro. Moreover, in wild-type mice, RSV prevented cardiac hypertrophy in response to hypertrophic stimuli...
March 1, 2015: American Journal of Physiology. Heart and Circulatory Physiology
https://www.readbyqxmd.com/read/25522270/resveratrol-regulates-mitochondrial-reactive-oxygen-species-homeostasis-through-sirt3-signaling-pathway-in-human-vascular-endothelial-cells
#15
X Zhou, M Chen, X Zeng, J Yang, H Deng, L Yi, M T Mi
Mitochondrial reactive oxygen species (mtROS) homeostasis plays an essential role in preventing oxidative injury in endothelial cells, an initial step in atherogenesis. Resveratrol (RSV) possesses a variety of cardioprotective activities, however, little is known regarding the effects of RSV on mtROS homeostasis in endothelial cells. Sirt3 is a mitochondrial deacetylase, which plays a key role in mitochondrial bioenergetics and is closely associated with oxidative stress. The goal of the study is to investigate whether RSV could attenuate oxidative injury in endothelial cells via mtROS homeostasis regulation through Sirt3 signaling pathway...
2014: Cell Death & Disease
https://www.readbyqxmd.com/read/24796938/sirt3-activation-attenuated-oxidized-low-density-lipoprotein-induced-human-umbilical-vein-endothelial-cells-apoptosis-by-sustaining-autophagy
#16
Xiandu Luo, Zhiqiang Yang, Shuai Zheng, Yong Cao, Yanqing Wu
Sirt3 is a central regulator of mitochondrial adaptation in health and disease. Our aim was to investigate the potential roles of Sirt3 in ox-LDL-treated endothelial cells. Short-term ox-LDL treatment of primary human umbilical vein endothelial cells (HUVECs) triggered autophagy, whereas long-term ox-LDL treatment resulted in apoptosis. Sirt3 expression consistently rose after short-term ox-LDL treatment and declined after long-term treatment of HUVECs. Pre-treatment with the Sirt3 activator resveratrol or Sirt3 overexpression enhanced autophagy and postponed HUVECs' apoptosis under long-term ox-LDL treatment...
May 5, 2014: Cell Biology International
https://www.readbyqxmd.com/read/24669285/antiaging-properties-of-a-grape-derived-antioxidant-are-regulated-by-mitochondrial-balance-of-fusion-and-fission-leading-to-mitophagy-triggered-by-a-signaling-network-of-sirt1-sirt3-foxo3-pink1-parkin
#17
Somak Das, Goran Mitrovsky, Hannah R Vasanthi, Dipak K Das
It was proposed that resveratrol, a polyphenolic antioxidant and a calorie restriction mimetic could promote longevity but subsequent studies could not prove this. The original proposal was based on the fact that a grape-derived antioxidant could activate the antiaging gene Sirt1. Most studies agree that indeed grape activates Sirt1, but a question remains whether Sirt1 is the cause or consequence of resveratrol treatment. Subsequently, mitochondrial Sirt3 was found to be activated. The present study on ischemic reperfusion (I/R) in rat hearts demonstrates that Foxo3a is activated subsequent to Sirt3 activation, which then activates PINK1...
2014: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/24606797/metabolic-reprogramming-of-human-cells-in-response-to-oxidative-stress-implications-in-the-pathophysiology-and-therapy-of-mitochondrial-diseases
#18
REVIEW
Yu-Ting Wu, Shi-Bei Wu, Yau-Huei Wei
Mitochondria are the organelles producing most of the energy and play important roles in a variety of biochemical functions in human cells. Mitochondrial defects can cause ATP deficiency and overproduction of reactive oxygen species, which are the major hallmarks of mitochondrial diseases. Abundant evidence has suggested that mitochondrial dysfunction-elicited oxidative stress can play an important role in the pathogenesis and progression of mitochondrial diseases. Mitochondria can respond to energy deficiency by the retrograde signaling to trigger a number of molecular events to help the human cells to cope with physiological or environmental changes...
2014: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/24211137/crystal-structures-of-sirt3-complexes-with-4-bromo-resveratrol-reveal-binding-sites-and-inhibition-mechanism
#19
Giang Thi Tuyet Nguyen, Melanie Gertz, Clemens Steegborn
Sirtuins are protein deacetylases regulating aging processes and various physiological functions. Resveratrol, a polyphenol found in red wine, activates human Sirt1 and inhibits Sirt3, and it can mimic calorie restriction effects, such as lifespan extension in lower organisms. The mechanism of Sirtuin modulation by resveratrol is not well understood. We used 4'-bromo-resveratrol (5-(2-(4-hydroxyphenyl)vinyl)-1,3-benzenediol) to study Sirt1 and Sirt3 modulation. Despite its similarity to the Sirt1 activator resveratrol, the compound potently inhibited both, Sirt1 and Sirt3...
November 21, 2013: Chemistry & Biology
https://www.readbyqxmd.com/read/24178296/resveratrol-induces-a-mitochondrial-complex-i-dependent-increase-in-nadh-oxidation-responsible-for-sirtuin-activation-in-liver-cells
#20
Valérie Desquiret-Dumas, Naïg Gueguen, Géraldine Leman, Stéphanie Baron, Valérie Nivet-Antoine, Stéphanie Chupin, Arnaud Chevrollier, Emilie Vessières, Audrey Ayer, Marc Ferré, Dominique Bonneau, Daniel Henrion, Pascal Reynier, Vincent Procaccio
Resveratrol (RSV) has been shown to be involved in the regulation of energetic metabolism, generating increasing interest in therapeutic use. SIRT1 has been described as the main target of RSV. However, recent reports have challenged the hypothesis of its direct activation by RSV, and the signaling pathways remain elusive. Here, the effects of RSV on mitochondrial metabolism are detailed both in vivo and in vitro using murine and cellular models and isolated enzymes. We demonstrate that low RSV doses (1-5 μM) directly stimulate NADH dehydrogenases and, more specifically, mitochondrial complex I activity (EC50 ∼1 μM)...
December 20, 2013: Journal of Biological Chemistry
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