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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
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...
January 18, 2017: Cellular Physiology and Biochemistry
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
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
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
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
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
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
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
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
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
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
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
Xiao-Feng Tian, Fu-Jian Ji, Hong-Liang Zang, Hong Cao
Liver fibrosis results from a sustained wound healing response to chronic liver injury, and the activation of nonparenchymal hepatic stellate cells (HSCs) is the pivotal process. MicroRNA-34a (miR-34a) is the direct target gene of p53 and activates p53 through sirtuin 1 (SIRT1) simultaneously. The miR-34a/SIRT1/p53 signaling pathway thus forms a positive feedback loop wherein p53 induces miR-34a and miR-34a activates p53 by inhibiting SIRT1, playing an important role in cell proliferation and apoptosis. miR-34a expression has been found to be increased in animal models or in human patients with different liver diseases, including liver fibrosis...
2016: PloS One
Bi Liu, Ming Lei, Tao Hu, Fei Yu, De-Ming Xiao, Hao Kang
SRT1720, a new discovered drug, was reported to activate silent information regulator 1 (SIRT1) and inhibit the chondrocyte apoptosis. However, the underlying mechanism remains elusive. In the present study, the chondrocytes were extracted from the cartilage tissues of New Zealand white rabbits, cultured in the presence of sodium nitroprusside (SNP) (2.5 mmol/L) and divided into five groups: 1, 5, 10, and 20 μmol/L SRT1720 groups and blank control group (0 μmol/L SRT1720). MTT assay was used to detect the chondrocyte viability and proliferation, and DAPI staining and flow cytometry to measure the chondrocyte apoptosis...
June 2016: Journal of Huazhong University of Science and Technology. Medical Sciences
Junpeng Liu, Weifeng Han, Lei Chen, Kanglai Tang
The aim of the present study was to assess the expression of sirtuin (Sirt)1 in tendon stem cells (TSCs) and to elucidate its association with osteogenic and adipogenic differentiation of TSCs. Reverse-transcription quantitative polymerase chain reaction (RT-qPCR) and western blot analyses were performed to detect Sirt1 mRNA and protein levels in TSCs, respectively. TSCs were positive for Sirt1 expression, which was elevated by Sirt1 activator SRT1720 in a time- and concentration- dependent manner, and decreased by Sirt1 inhibitor EX527...
August 2016: Molecular Medicine Reports
Stijntje Hibender, Romy Franken, Cindy van Roomen, Anique Ter Braake, Ingeborg van der Made, Edith E Schermer, Quinn Gunst, Maurice J van den Hoff, Esther Lutgens, Yigal M Pinto, Maarten Groenink, Aeilko H Zwinderman, Barbara J M Mulder, Carlie J M de Vries, Vivian de Waard
OBJECTIVE: Marfan syndrome (MFS) is a connective tissue disorder caused by mutations in the fibrillin-1 gene. Patients with MFS are at risk of aortic aneurysm formation and dissection. Usually, blood pressure-lowering drugs are used to reduce aortic events; however, this is not sufficient for most patients. In the aorta of smooth muscle cell-specific sirtuin-1-deficient mice, spontaneous aneurysm formation and senescence are observed. Resveratrol is known to enhance sirtuin-1 activity and to reduce senescence, which prompted us to investigate the effectiveness of resveratrol in inhibition of aortic dilatation in the Fbn1(C1039G/+) MFS mouse model...
August 2016: Arteriosclerosis, Thrombosis, and Vascular Biology
Jai Won Chang, Hyosang Kim, Chung Hee Baek, Raymond Bok Lee, Won Seok Yang, Sang Koo Lee
BACKGROUND: Endoplasmic reticulum (ER) stress is emerging as an important factor in the development of organ fibrosis. Therefore, modulation of ER stress may serve as one of the possible therapeutic approaches to renal fibrosis. SIRT1, a class III histone deacetylase, has been found to exert beneficial effects in kidney diseases. However, it is largely unknown whether and how SIRT1 suppresses the ER stress. We postulated that upregulation of SIRT1 would suppress the ER stress through induction of heme oxygenase-1 (HO-1) and thioredoxin...
2016: Nephron
William R Swindell, Xianying Xing, Yi Fritz, Doina Diaconu, Daniel I Simon, Nicole L Ward, Johann E Gudjonsson
The Mrp8 and Mrp14 proteins (calprotectin) accumulate within tissues during aging and may contribute to chronic inflammation. To address this possibility, we evaluated female calprotectin-deficient Mrp14-KO and wild-type (WT) mice at 5 and 24 months of age. However, there was no evidence that age-related inflammation is blunted in KO mice. Inflammation markers were in fact elevated in livers from old KO mice, and microarray analysis revealed more consistent elevation of genes specifically expressed by B-cells and T-cells...
June 14, 2016: Oncotarget
Kellie E Cunningham, Garret Vincent, Chhinder P Sodhi, Elizabeth A Novak, Sarangarajan Ranganathan, Charlotte E Egan, Donna Beer Stolz, Matthew B Rogers, Brian Firek, Michael J Morowitz, George K Gittes, Brian S Zuckerbraun, David J Hackam, Kevin P Mollen
Peroxisome proliferator-activated receptor-γ coactivator 1-α (PGC1α) is the primary regulator of mitochondrial biogenesis and was recently found to be highly expressed within the intestinal epithelium. PGC1α is decreased in the intestinal epithelium of patients with inflammatory bowel disease, but its role in pathogenesis is uncertain. We now hypothesize that PGC1α protects against the development of colitis and helps to maintain the integrity of the intestinal barrier. We selectively deleted PGC1α from the intestinal epithelium of mice by breeding a PGC1α(loxP/loxP) mouse with a villin-cre mouse...
May 6, 2016: Journal of Biological Chemistry
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