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https://www.readbyqxmd.com/read/29209448/sirt1-protects-endothelial-cells-against-lps-induced-barrier-dysfunction
#1
Weijin Zhang, Yaoyuan Zhang, Xiaohua Guo, Zhenhua Zeng, Jie Wu, Yanan Liu, Jing He, Ruiting Wang, Qiaobing Huang, Zhongqing Chen
Sepsis is a threatening health problem and characterized by microvascular dysfunction. In this study, we verified that LPS caused the downregulation of Sirt1 and the hyperpermeability of endothelial cells. Inhibition of Sirt1 with ex527 or Sirt1 siRNA displayed a higher permeability, while activation of Sirt1 with SRT1720 reversed the LPS-induced hyperpermeability, formation of fiber stress, and disruption of VE-cadherin distribution. In pulmonary microvascular vein endothelial cells isolated from wild-type mice, Sirt1 was attenuated upon LPS, while Sirt1 was preserved in a receptor of advanced glycation end product-knockout mice...
2017: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/29134718/sirt1-exhibits-antioxidative-effects-in-ht22-cells-induced-by-tert-butyl-alcohol
#2
Junxiang Ma, Dongmei Song, Yuanyuan Zhang, Li Chen, Shixuan Zhang, Jiaxin Jia, Tian Chen, Caixia Guo, Lin Tian, Ai Gao, Piye Niu
Tertiary butyl alcohol (TBA) is a principal metabolite of methyl tertiary-butyl ether (MTBE), a common pollutant worldwide in the ground or underground water, which is found to produce nervous system damage. Nevertheless, few data regarding the effects of TBA has been reported. Studies indicated that oxidative stress plays a pivotal role in MTBE neurotoxic mechanism. Sirtuin 1 (SIRT1) has been reported to exert a neuroprotective effect on various neurologic diseases via resistance to oxidative stress by deacetylating its substrates...
November 14, 2017: Environmental Toxicology
https://www.readbyqxmd.com/read/29078895/srt1720-a-sirtuin-1-activator-attenuates-organ-injury-and-inflammation-in-sepsis
#3
Adam Khader, Weng-Lang Yang, Laura W Hansen, Salil R Rajayer, Jose M Prince, Jeffrey M Nicastro, Gene F Coppa, Ping Wang
BACKGROUND: Sepsis affects 800,000 patients in the United States annually with a mortality rate of up to 30%. Recent studies suggest that sepsis-associated metabolic derangements due to hypoxic tissue injury, impaired oxygen utilization, and mitochondrial dysfunction contribute to mortality. Sirtuin 1 (Sirt1) is a crucial modulator of energy metabolism during starvation states and has anti-inflammatory effects. Here, we hypothesized that SRT1720, a Sirt1 activator, could attenuate the severity of sepsis...
November 2017: Journal of Surgical Research
https://www.readbyqxmd.com/read/29059204/alterations-of-sirtuins-in-mitochondrial-cytochrome-c-oxidase-deficiency
#4
Arne Björn Potthast, Theresa Heuer, Simone Johanna Warneke, Anibh Martin Das
BACKGROUND: Sirtuins are NAD+ dependent deacetylases, which regulate mitochondrial energy metabolism as well as cellular response to stress. The NAD/NADH-system plays a crucial role in oxidative phosphorylation linking sirtuins and the mitochondrial respiratory chain. Furthermore, sirtuins are able to directly deacetylate and activate different complexes of the respiratory chain. This prompted us to analyse sirtuin levels in skin fibroblasts from patients with cytochrome c-oxidase (COX) deficiency and to test the impact of different pharmaceutical activators of sirtuins (SRT1720, paeonol) to modulate sirtuins and possibly respiratory chain enzymes in patient cells in vitro...
2017: PloS One
https://www.readbyqxmd.com/read/28968596/resveratrol-inhibits-the-epidermal-growth-factor-induced-migration-of-osteoblasts-the-suppression-of-sapk-jnk-and-akt
#5
Tetsu Kawabata, Haruhiko Tokuda, Kazuhiko Fujita, Shingo Kainuma, Go Sakai, Rie Matsushima-Nishiwaki, Osamu Kozawa, Takanobu Otsuka
BACKGROUND/AIMS: Resveratrol is a polyphenol enriched in the skins of grapes and berries, that shows various beneficial effects for human health. In the present study, we investigated the mechanism behind the epidermal growth factor (EGF)-induced migration of osteoblast-like MC3T3-E1 cells, and the effect of resveratrol on this cell migration. METHODS: The cell migration was examined using Boyden chamber, and phosphorylation of each kinase was analyzed by Western blotting...
2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28937996/sirt1-is-a-positive-regulator-of-in-vivo-bone-mass-and-a-therapeutic-target-for-osteoporosis
#6
Kayvan Zainabadi, Cassie J Liu, Alison L M Caldwell, Leonard Guarente
Overexpression or pharmacological activation of SIRT1 has been shown to extend the lifespan of mice and protect against aging-related diseases. Here we show that pharmacological activation of SIRT1 protects in two models of osteoporosis. Ovariectomized female mice and aged male mice, models for post-menopausal and aging-related osteoporosis, respectively, show significant improvements in bone mass upon treatment with SIRT1 agonist, SRT1720. Further, we find that calorie restriction (CR) results in a two-fold upregulation of sirt1 mRNA expression in bone tissue that is associated with increased bone mass in CR mice...
2017: PloS One
https://www.readbyqxmd.com/read/28827156/induction-of-mitochondrial-biogenesis-protects-against-acetaminophen-hepatotoxicity
#7
Kuo Du, Anup Ramachandran, Mitchell R McGill, Abdellah Mansouri, Tarik Asselah, Anwar Farhood, Benjamin L Woolbright, Wen-Xing Ding, Hartmut Jaeschke
Mitochondrial biogenesis (MB) is an adaptive response to maintain metabolic homeostasis after mitochondrial dysfunction. Induction of MB during APAP hepatotoxicity has not been studied. To investigate this, mice were treated with toxic doses of APAP and euthanized between 0 and 96 h. At early time points, APAP caused both mitochondrial dysfunction and reduction of mitochondrial mass, indicated by reduced activity of electron transport chain (ETC) complexes I and IV and depletion of mitochondrial DNA (mtDNA), respectively...
October 2017: Food and Chemical Toxicology
https://www.readbyqxmd.com/read/28776729/sirt1-activates-the-expression-of-fetal-hemoglobin-genes
#8
Yan Dai, Tyngwei Chen, Heba Ijaz, Elizabeth H Cho, Martin H Steinberg
High fetal hemoglobin (HbF, α2 γ2 ) levels ameliorate the clinical manifestations of sickle cell disease and β thalassemia. The mechanisms that repress HbF expression and silence γ-globin genes in adults are incompletely characterized and only a single HbF inducer, hydroxyurea, is approved for treatment, and only in patients with sickle cell disease. We identified SIRT1, a protein deacetylase, as a new inducer of γ-globin. SIRT1 knockdown decreased, while SIRT1 ectopic expression upregulated γ-globin gene (HBG) expression in primary human erythroid cells and in K562 cells...
November 2017: American Journal of Hematology
https://www.readbyqxmd.com/read/28693188/consecutive-stimulation-of-hbsag-promotes-the-viability-of-the-human-b-lymphoblastoid-cell-line-im-9-through-regulating-the-sirt1-nf-%C3%AE%C2%BAb-pathway
#9
Jian Bo, Xiaojuan Wang, Jie Li, Wenqing Wang, Jinqian Zhang
Patients with chronic HBV infection have been reported to suffer a significantly increased risk of NHL, but the underlying mechanisms remain to be clearly explained. The aim of the present study was to clarify the relationship between chronic HBV infection and NHL development. Fluorescence-activated cell sorting, Annexin V/7-aminoactinomycin D staining and MTS assay were used to analyze the rate of apoptosis and cell viability. In addition, western blotting was used to detect protein expression. The effects of the activator of SIRT1, SRT1720, and the inhibitor of SIRT1, nicotinamide, were also analyzed...
July 2017: Oncology Letters
https://www.readbyqxmd.com/read/28681509/akt2-ablation-prolongs-life-span-and-improves-myocardial-contractile-function-with-adaptive-cardiac-remodeling-role-of-sirt1-mediated-autophagy-regulation
#10
Jun Ren, Lifang Yang, Li Zhu, Xihui Xu, Asli F Ceylan, Wei Guo, Jian Yang, Yingmei Zhang
Aging is accompanied with unfavorable geometric and functional changes in the heart involving dysregulation of Akt and autophagy. This study examined the impact of Akt2 ablation on life span and cardiac aging as well as the mechanisms involved with a focus on autophagy and mitochondrial integrity. Cardiac geometry, contractile, and intracellular Ca(2+) properties were evaluated using echocardiography, IonOptix(®) edge-detection and fura-2 techniques. Levels of Sirt1, mitochondrial integrity, autophagy, and mitophagy markers were evaluated using Western blot...
October 2017: Aging Cell
https://www.readbyqxmd.com/read/28677796/resveratrol-suppresses-thyroid-hormone%C3%A2-induced-osteocalcin-synthesis-in-osteoblasts
#11
Kazuhiko Fujita, Haruhiko Tokuda, Shingo Kainuma, Gen Kuroyanagi, Naohiro Yamamoto, Rie Matsushima-Nishiwaki, Atsushi Harada, Osamu Kozawa, Takanobu Otsuka
Resveratrol, a polyphenolic compound that is present in grape skins, berries and red wine, may be beneficial for human health through its anti‑inflammatory and anti‑oxidant effects. It has been previously demonstrated that resveratrol exerts its biological effects primarily via sirtuin 1 (SIRT1) activation. We previously reported that triiodothyronine (T3) induces osteocalcin synthesis in osteoblast‑like MC3T3‑E1 cells, and that p38 mitogen‑activated protein (MAP) kinase mediates the T3‑stimulated synthesis of osteocalcin...
September 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28579512/homocysteine-up-regulates-endothelin-type-a-receptor-in-vascular-smooth-muscle-cells-through-sirt1-erk1-2-signaling-pathway
#12
Yulong Chen, Huanhuan Liu, Xinhong Wang, Hongmei Zhang, Enqi Liu, Xingli Su
Sirtuin 1 (Sirt1) is a longevity gene that has protective effects in cardiovascular diseases (CVDs). The endothelin type A (ETA) receptor is involved in pathogenesis of CVDs. The extracellular signal related kinases 1 and 2 (ERK1/2) signaling pathway is involved in regulation of the ETA receptor induced by some CVD risk factors in vascular smooth muscle cells (VSMCs). Hyperhomocysteinemia (HHcy) is an independent risk factor for CVDs. The present study was designed to investigate the hypothesis that homocysteine up-regulates ETA receptor through the Sirt1/ERK1/2 signaling pathway...
June 1, 2017: Microvascular Research
https://www.readbyqxmd.com/read/28553227/srt1720-alleviates-anit-induced-cholestasis-in-a-mouse-model
#13
Linxi Yu, Xiaoxin Liu, Zihang Yuan, Xiaojiaoyang Li, Hang Yang, Ziqiao Yuan, Lixin Sun, Luyong Zhang, Zhengzhou Jiang
Intrahepatic cholestasis is a kind of clinical syndrome along with hepatotoxicity which caused by intrahepatic and systemic accumulations of bile acid. There are several crucial generating factors of the pathogenesis of cholestasis, such as inflammation, dysregulation of bile acid transporters and oxidative stress. SIRT1 is regarded as a class III histone deacetylase (HDAC). According to a set of researches, SIRT1 is one of the most important factors which can regulate the hepatic bile acid metabolism. SRT1720 is a kind of activator of SIRT1 which is 1000 times more potent than resveratrol, and this paper is aimed to study its protective influence on hepatotoxicity and cholestasis induced by alpha-naphthylisothiocyanate (ANIT) in mice...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28536529/activation-of-sirt1-fxr-signaling-pathway-attenuates-triptolide-induced-hepatotoxicity-in-rats
#14
Jing Yang, Lixin Sun, Lu Wang, Hozeifa M Hassan, Xuan Wang, Phillip B Hylemon, Tao Wang, Huiping Zhou, Luyong Zhang, Zhenzhou Jiang
Triptolide (TP), a diterpenoid isolated from Tripterygium wilfordii Hook F, has an excellent pharmacological profile of immunosuppression and anti-tumor activities, but its clinical applications are severely restricted due to its severe and cumulative toxicities. The farnesoid X receptor (FXR) is the master bile acid nuclear receptor and plays an important role in maintaining hepatic metabolism homeostasis. Hepatic Sirtuin (Sirt1) is a key regulator of the FXR signaling pathway and hepatic metabolism homeostasis...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28494457/resveratrol-protects-against-pulmonary-arterial-hypertension-in-rats-via-activation-of-silent-information-regulator-1
#15
Lei Yu, Yingfeng Tu, Xueling Jia, Kun Fang, Li Liu, Lin Wan, Chuanying Xiang, Yanan Wang, Xiangju Sun, Tianyou Liu, Dejun Yu, Weiwei Cao, Yinli Song, Yuhua Fan
BACKGROUND/OBJECTIVES: The polyphenol resveratrol (Rev) has been found to exhibit various beneficial effects including prevention of pulmonary arterial hypertension (PAH). The present study was designed to investigate the action and potential mechanism of Rev on PAH, focusing on the role of SIRT1 (Silent Information Regulator 1) in apoptosis of pulmonary artery smooth muscle cells (PASMCs). METHODS: PAH rats were established by exposure to hypoxia for 21 days. Rev and SRT1720 (a selective SIRT1 activator) were used to reverse PAH by gavaging rats...
2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28396013/specific-sirt1-activator-mediated-improvement-in-glucose-homeostasis-requires-sirt1-independent-activation-of-ampk
#16
Sung-Jun Park, Faiyaz Ahmad, Jee-Hyun Um, Alexandra L Brown, Xihui Xu, Hyeog Kang, Hengming Ke, Xuesong Feng, James Ryall, Andrew Philp, Simon Schenk, Myung K Kim, Vittorio Sartorelli, Jay H Chung
The specific Sirt1 activator SRT1720 increases mitochondrial function in skeletal muscle, presumably by activating Sirt1. However, Sirt1 gain of function does not increase mitochondrial function, which raises a question about the central role of Sirt1 in SRT1720 action. Moreover, it is believed that the metabolic effects of SRT1720 occur independently of AMP-activated protein kinase (AMPK), an important metabolic regulator that increases mitochondrial function. Here, we show that SRT1720 activates AMPK in a Sirt1-independent manner and SRT1720 activates AMPK by inhibiting a cAMP degrading phosphodiesterase (PDE) in a competitive manner...
April 2017: EBioMedicine
https://www.readbyqxmd.com/read/28383554/srt1720-promotes-survival-of-aged-human-mesenchymal-stem-cells-via-faim-a-pharmacological-strategy-to-improve-stem-cell-based-therapy-for-rat-myocardial-infarction
#17
Xianbao Liu, Dexing Hu, Zhiru Zeng, Wei Zhu, Na Zhang, Hong Yu, Han Chen, Kan Wang, Yingchao Wang, Lengmei Wang, Jing Zhao, Ling Zhang, Rongrong Wu, Xinyang Hu, Jian'an Wang
SIRT1 has been proved to rejuvenate and improve the therapeutic efficacy of aged rat mesenchymal stem cells (MSCs). Herein, we investigate the protective effect of pretreatment with SIRT1 activator SRT1720 on aged human MSCs (hMSCs). The optimized pretreatment condition for aged hMSCs was determined to be 0.5 μM SRT1720 for 24 h by monitoring the survival of aged hMSCs subjected to serum deprivation±hypoxia and±500 μM hydrogen peroxide (H2O2). Pretreatment with these conditions increased the survival of aged hMSCs 1 day (2...
April 6, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28360860/acanthoic-acid-can-partially-prevent-alcohol-exposure-induced-liver-lipid-deposition-and-inflammation
#18
You-Li Yao, Xin Han, Zhi-Man Li, Li-Hua Lian, Ji-Xing Nan, Yan-Ling Wu
Aims: The present study aims to detect the effect of acanthoic acid (AA) on alcohol exposure-induced liver lipid deposition and inflammation, and to explore the mechanisms. Methods: C57BL/6 mice were pretreated with single dose of AA (20 and 40 mg/kg) by oral gavage or equal volume of saline, and then exposed to three doses of ethanol (5 g/kg body weight, 25%, w/v) by gavage within 24 h. The mice were sacrificed at 6 h after the last ethanol dosing. Serum and hepatic indexes were detected by western blot, RT-PCR, and histopathological assay...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28339034/the-sirt1-activator-srt1720-attenuates-renal-fibrosis-by-inhibiting-ctgf-and-oxidative-stress
#19
Yunzhuo Ren, Chunyang Du, Yonghong Shi, Jingying Wei, Haijiang Wu, Huixian Cui
The transforming growth factor-β1 (TGF-β1)/connective tissue growth factor (CTGF) pathway plays an important role in the pathogenesis and progression of chronic kidney disease. Oxidative stress is also involved in TGF-β1 signalling. Sirtuin 1 (Sirt1) exerts a number of pleiotropic effects, protecting against renal disease, including inhibiting fibrosis and oxidative metabolism. In this study, we investigated the role of the Sirt1 activator, SRT1720, in unilateral ureteral obstruction (UUO)-induced tubulointerstitial fibrosis and aimed to determine whether this role depends on the inhibition of oxidative stress and the TGF-β1/CTGF pathway...
May 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/28336124/ultraviolet-b-inhibition-of-dnmt1-activity-via-ahr-activation-dependent-sirt1-suppression-in-cd4-t-cells-from-systemic-lupus-erythematosus-patients
#20
Zhouwei Wu, Xingyu Mei, Zuolin Ying, Yue Sun, Jun Song, Weimin Shi
BACKGROUND: Previous studies have reported that ultraviolet B (UVB) inhibits DNA methyltransferase1 (DNMT1) activity in CD4+ T cells from systemic lupus erythematosus (SLE) patients. Silent mating type information regulation 2 homolog 1 (SIRT1) is a type of Class III histone deacetylases (HDACs), and has been reported to play roles in the pathogenesis of different autoimmune diseases and can modulate DNMT1 activity. Moreover, aryl hydrocarbon receptor (AhR) has been reported to link UVB with SLE...
June 2017: Journal of Dermatological Science
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