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https://www.readbyqxmd.com/read/28536529/activation-of-sirt1-fxr-signaling-pathway-attenuates-triptolide-induced-hepatotoxicity-in-rats
#1
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
#2
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...
May 11, 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
#3
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
#4
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
#5
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
#6
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...
March 22, 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
#7
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
#8
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
#9
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
#10
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 investigated the effect of SIRT1 in SCI using pharmacological intervention (SRT1720) and the Mx1-Cre/loxP recombination system to knock out target genes...
February 13, 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
#11
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
#12
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
#13
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
#14
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
https://www.readbyqxmd.com/read/27749604/sirt1-attenuates-neuropathic-pain-by-epigenetic-regulation-of-mglur1-5-expressions-in-type-2-diabetic-rats
#15
Cheng-Hua Zhou, Ming-Xing Zhang, Sha-Sha Zhou, Huan Li, Jian Gao, Lei Du, Xiao-Xing Yin
Accumulating evidence has demonstrated that epigenetic modification-mediated changes in pain-related gene expressions play an important role in the development and maintenance of neuropathic pain. Sirtuin 1 (SIRT1), a nicotinamide adenine dinucleotide (NAD)-dependent deacetylase, is involved in the development of chronic pain. Moreover, SIRT1 may be a novel therapeutic target for the prevention of type 2 diabetes mellitus (T2DM). But the role of SIRT1 in T2DM-induced neuropathic pain remains unknown. In this study, we found that spinal SIRT1 expression and activity were downregulated significantly in high-fat-fed/low-dose streptozotocin-induced neuropathic pain rats...
January 2017: Pain
https://www.readbyqxmd.com/read/27639250/sirtuin-1-activation-alleviates-cholestatic-liver-injury-in-a-cholic-acid-fed-mouse-model-of-cholestasis
#16
Supriya R Kulkarni, Carol J Soroka, Lee R Hagey, James L Boyer
Sirtuin1 (Sirt1; mammalian homolog of Saccharomyces cerevisiae enzyme Sir2) is a transcriptional and transactivational regulator of murine farnesoid X receptor (Fxr), which is the primary bile acid (BA) sensor, and critical regulator of BA metabolism in physiological and pathophysiological conditions. Previous studies have suggested compromised Sirt1 expression in rodent models of cholestatic liver injury. We hypothesized that Sirt1 could be potentially targeted to alleviate cholestatic liver injury. In cultured primary human hepatocytes, SIRT1 messenger RNA was down-regulated after GCA treatment, potentially through induction of microRNA (miR)-34a, whereas tauroursodeoxycholic acid induced SIRT1 expression without affecting miR-34a expression...
December 2016: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/27620389/activation-of-sirt1-attenuates-klotho-deficiency-induced-arterial-stiffness-and-hypertension-by-enhancing-amp-activated-protein-kinase-activity
#17
Diansa Gao, Zhong Zuo, Jing Tian, Quaisar Ali, Yi Lin, Han Lei, Zhongjie Sun
Arterial stiffness is an independent risk factor for stroke and myocardial infarction. This study was designed to investigate the role of SIRT1, an important deacetylase, and its relationship with Klotho, a kidney-derived aging-suppressor protein, in the pathogenesis of arterial stiffness and hypertension. We found that the serum level of Klotho was decreased by ≈45% in patients with arterial stiffness and hypertension. Interestingly, Klotho haplodeficiency caused arterial stiffening and hypertension, as evidenced by significant increases in pulse wave velocity and blood pressure in Klotho-haplodeficient (KL(+/-)) mice...
November 2016: Hypertension
https://www.readbyqxmd.com/read/27564107/sirt1-mediated-foxos-pathways-protect-against-apoptosis-by-promoting-autophagy-in-osteoblast-like-mc3t3-e1-cells-exposed-to-sodium-fluoride
#18
Xiaolong Gu, Dandan Han, Wei Chen, Limei Zhang, Qianyun Lin, Jian Gao, Séamus Fanning, Bo Han
Fluorine may result in damage to teeth, bones and other body tissues, and is a serious public health problem. SIRT1 deacetylates FOXOs, which brings about apoptosis and autophagy promotion or suppression. Fluorine may induce cell apoptosis, however, the role of autophagy in apoptosis induced by fluorine is still poorly understood, and the interaction between SIRT1 and FOXOs should be further illustrated. Therefore, this study investigated the mechanisms underlying the NaF- induced apoptosis and autophagy in osteoblast-like MC3T3-E1 cells in vitro through activating or inhibiting SIRT1...
October 4, 2016: Oncotarget
https://www.readbyqxmd.com/read/27508009/srt1720-a-sirt1-specific-activator-protected-h2o2-induced-senescent-endothelium
#19
Rui-Lin Li, Zhao-Yang Lu, Jing-Juan Huang, Jia Qi, An Hu, Zhi-Xiao Su, Lan Zhang, Yue Li, Yi-Qin Shi, Chang-Ning Hao, Jun-Li Duan
Silent information regulator 1 (SIRT1) plays a critical role in maintaining vascular homeostasis via modulating senescent-related signal pathway, however, the molecular mechanism remains modest clarified. The purpose of this study was to examine whether SIRT1 specific activator SRT1720 would exhibit pro-angiogenic and anti-aging properties in response to hydrogen peroxide (H2O2)-induced endothelial senescence, and determine the underlying mechanisms. We pre-treated senescent human umbilical vein endothelial cells (HUVECs) with SRT1720, senescence-associated beta-galactosidase activity, apoptosis, migration, tube formation, proliferation and angiogenic factors were quantitatively examined...
2016: American Journal of Translational Research
https://www.readbyqxmd.com/read/27432859/vascular-smooth-muscle-sirtuin-1-protects-against-diet-induced-aortic-stiffness
#20
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
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