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https://www.readbyqxmd.com/read/28776729/sirt1-activates-the-expression-of-fetal-hemoglobin-genes
#1
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...
August 4, 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
#2
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
#3
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...
July 5, 2017: Aging Cell
https://www.readbyqxmd.com/read/28677796/resveratrol-suppresses-thyroid-hormone%C3%A2-induced-osteocalcin-synthesis-in-osteoblasts
#4
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
#5
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
#6
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
#7
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
#8
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
#9
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
#10
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
#11
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
#12
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
#13
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
https://www.readbyqxmd.com/read/28248534/sirtuin-activating-compounds-stacs-alleviate-d-galactosamine-lipopolysaccharide-induced-hepatotoxicity-in-rats-involvement-of-sirtuin-1-and-heme-oxygenase-1
#14
M K Kemelo, N Kutinová Canová, A Horinek, H Farghali
Sirtuin activating compounds (STACs) attenuate various type of liver insults through mechanisms which are not fully understood. In the present study, we investigated the ameliorative potential of quercetin (natural polyphenol) and SRT1720 (synthetic SIRT1 activator) against D-galactosamine/lipopolysaccharide-induced hepatotoxicity (an experimental model of acute liver failure). Moreover, we compared and contrasted the roles of stress responsive enzymes, sirtuin 1 (SIRT1) and heme oxygenase 1 (HO-1) in hepatoprotection/ hepatotoxicity...
February 28, 2017: Physiological Research
https://www.readbyqxmd.com/read/28214900/mir-21-regulates-tnf-%C3%AE-induced-cd40-expression-via-the-sirt1-nf-%C3%AE%C2%BAb-pathway-in-renal-inner-medullary-collecting-duct-cells
#15
Qinqin Lin, Yuanwen Geng, Meng Zhao, Shuaishuai Lin, Qing Zhu, Zhenjun Tian
BACKGROUND/AIMS: Recent studies have indicated that microRNA-21 (miR-21) is involved in the inflammatory response in relation to renal disease. Sirtuin1 (SIRT1) exerts renoprotective properties by counteracting inflammation. The activation of CD40 triggers inflammation that participates in renal inflammation and injury. The relationship between miR-21, SIRT1 and CD40, however, remains elusive. METHODS: Immunohistochemistry, small-interfering RNA (siRNA) transfection, quantitative real-time PCR and western blotting were applied to assess the morphological, functional and molecular mechanisms in primary cultured renal inner medullary collecting duct (IMCD) cells...
2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28193684/an-agonist-of-the-protective-factor-sirt1-improves-functional-recovery-and-promotes-neuronal-survival-by-attenuating-inflammation-after-spinal-cord-injury
#16
Haihong Chen, Hao Ji, Ming Zhang, Zude Liu, Lifeng Lao, Chao Deng, Jianwei Chen, Guibin Zhong
Targeting posttraumatic inflammation is crucial for improving locomotor function. SIRT1 has been shown to play a critical role in disease processes such as hepatic inflammation, rheumatoid arthritis, and acute lung inflammation by regulating inflammation. However, the role of SIRT1 in spinal cord injury (SCI) is unknown. We hypothesized that SIRT1 plays an important role in improving locomotor function after SCI by regulating neuroinflammation. In this study, we investigate the effect of SIRT1 in SCI using pharmacological intervention (SRT1720) and the Mx1-Cre/loxP recombination system to knock out target genes...
March 15, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/27980322/sirtuin1-sirt1-regulates-tumor-necrosis-factor-alpha-tnf-%C3%AE-induced-aquaporin-2-aqp2-expression-in-renal-medullary-collecting-duct-cells-through-inhibiting-the-nf-%C3%AE%C2%BAb-pathway
#17
Qinqin Lin, Yuanwen Geng, Shuaishuai Lin, Zhenjun Tian
BACKGROUND Aquaporin-2 (AQP2) plays a major role in water reabsorption in the renal collecting duct, and is involved in a variety of renal disease. Recent studies have indicate that sirtuin1 (SIRT1) exerts renoprotective properties against kidney diseases. This study aimed to determine the potential role of SIRT1 in AQP2 expression induced by tumor necrosis factor-alpha (TNF-α) and to disclose the underlying mechanism in renal inner medullary collecting duct (IMCD) cells. MATERIAL AND METHODS Quantitative real-time PCR and Western blotting were respectively identified mRNA and protein expression...
December 16, 2016: Medical Science Monitor Basic Research
https://www.readbyqxmd.com/read/27916733/sirt1-regulates-lipopolysaccharide-induced-cd40-expression-in-renal-medullary-collecting-duct-cells-by-suppressing-the-tlr4-nf-%C3%AE%C2%BAb-signaling-pathway
#18
Qin-Qin Lin, Yuan-Wen Geng, Zhong-Wei Jiang, Zhen-Jun Tian
AIMS: Recent evidence indicates that sirtuin1 (SIRT1), an NAD(+)-dependent deacetylase, exerts a protective effect against inflammatory kidney injury by suppressing pro-inflammatory cytokines production. The co-stimulatory molecule, CD40, is expressed in a variety of inflammatory diseases in the kidney. Here, we aimed to investigate the potential effect of SIRT1 on CD40 expression induced by lipopolysaccharide (LPS) and to disclose the underlying mechanisms in renal inner medullary collecting duct (IMCD) cells...
February 1, 2017: Life Sciences
https://www.readbyqxmd.com/read/27818225/protective-effects-of-srt1720-via-the-hnf1%C3%AE-fxr-signalling-pathway-and-anti-inflammatory-mechanisms-in-mice-with-estrogen-induced-cholestatic-liver-injury
#19
Linxi Yu, Xiaoxin Liu, Xiaojiaoyang Li, Zihang Yuan, Hang Yang, Luyong Zhang, Zhenzhou Jiang
Sirtuin 1 (SIRT1) is the most conserved mammalian NAD(+)-dependent protein deacetylase and is a member of the silent information regulator 2 (Sir2) families of proteins (also known as Sirtuins). In the liver, hepatic SIRT1 modulates bile acid metabolism through the regulation of farnesoid X receptor (FXR) expression. FXR is one of the most important nuclear receptors involved in the regulation of bile acid metabolism. SIRT1 modulates the FXR expression at multiple levels, including direct deacetylation of this transcription factor and transcriptional regulation through hepatocyte nuclear factor 1α (HNF1α)...
December 15, 2016: Toxicology Letters
https://www.readbyqxmd.com/read/27764247/sirt1-pgc1%C3%AE-nf%C3%AE%C2%BAb-pathway-of-oxidative-and-inflammatory-stress-during-trypanosoma-cruzi-infection-benefits-of-sirt1-targeted-therapy-in-improving-heart-function-in-chagas-disease
#20
Xianxiu Wan, Jian-Jun Wen, Sue-Jie Koo, Lisa Yi Liang, Nisha Jain Garg
Chronic chagasic cardiomyopathy (CCM) is presented by increased oxidative/inflammatory stress and decreased mitochondrial bioenergetics. SIRT1 senses the redox changes and integrates mitochondrial metabolism and inflammation; and SIRT1 deficiency may be a major determinant in CCM. To test this, C57BL/6 mice were infected with Trypanosoma cruzi (Tc), treated with SIRT1 agonists (resveratrol or SRT1720), and monitored during chronic phase (~150 days post-infection). Resveratrol treatment was partially beneficial in controlling the pathologic processes in Chagas disease...
October 2016: PLoS Pathogens
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