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Sirtuins

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https://www.readbyqxmd.com/read/29787963/sirt1-activator-e1231-protects-from-experimental-atherosclerosis-and-lowers-plasma-cholesterol-and-triglycerides-by-enhancing-abca1-expression
#1
Tingting Feng, Peng Liu, Xiao Wang, Jinque Luo, Xuan Zuo, Xinhai Jiang, Chang Liu, Yongzhen Li, Ni Li, Minghua Chen, Ningyu Zhu, Xiaowan Han, Chao Liu, Yanni Xu, Shuyi Si
BACKGROUND AND AIMS: Sirtuin 1 (SIRT1) is a nicotinamide adenine dinucleotide-dependent protein deacetylase. Recent studies have demonstrated that enhancing SIRT1 expression or activity may modulate cholesterol and lipid metabolism. However, pharmacological and molecular regulators for SIRT1 are scarce. Here, we aimed to find novel small molecule modulators of SIRT1 to regulate cholesterol and lipid metabolism. METHODS: A high-throughput screening assay was established to identify SIRT1 activators...
April 30, 2018: Atherosclerosis
https://www.readbyqxmd.com/read/29786646/metabolic-reprogramming-by-3-iodothyronamine-t1am-a-new-perspective-to-reverse-obesity-through-co-regulation-of-sirtuin-4-and-6-expression
#2
Fariba M Assadi-Porter, Hannah Reiland, Martina Sabatini, Leonardo Lorenzini, Vittoria Carnicelli, Micheal Rogowski, Ebru S Selen Alpergin, Marco Tonelli, Sandra Ghelardoni, Alessandro Saba, Riccardo Zucchi, Grazia Chiellini
Obesity is a complex disease associated with environmental and genetic factors. 3-Iodothyronamine (T1AM) has revealed great potential as an effective weight loss drug. We used metabolomics and associated transcriptional gene and protein expression analysis to investigate the tissue specific metabolic reprogramming effects of subchronic T1AM treatment at two pharmacological daily doses (10 and 25 mg/kg) on targeted metabolic pathways. Multi-analytical results indicated that T1AM at 25 mg/kg can act as a novel master regulator of both glucose and lipid metabolism in mice through sirtuin-mediated pathways...
May 22, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29784872/sirt1-inhibits-rheumatoid-arthritis-fibroblast-like-synoviocyte-aggressiveness-and-inflammatory-response-via-suppressing-nf-%C3%AE%C2%BAb-pathway
#3
Guoqing Li, Zhongbing Xia, Ying Liu, Fanru Meng, Xia Wu, Yuxuan Fang, Chunwang Zhang, Dan Liu
Rheumatoid arthritis (RA) is an autoimmune disease of the joints characterized by synovial hyperplasia and chronic inflammation. Fibroblast-like synoviocytes (FLS) play a central role in RA initiation, progression, and perpetuation. Prior studies showed that sirtuin 1(SIRT1), a deacetylase participating in a broad range of transcriptional and metabolic regulations, may impact cell proliferation and inflammatory responses. However, the role of SIRT1 in RA-FLS was unclear. Here, we explored the effects of SIRT1 on the aggressiveness and inflammatory responses of cultured RA-FLS...
May 21, 2018: Bioscience Reports
https://www.readbyqxmd.com/read/29783884/roles-of-progesterone-receptor-membrane-component-1-in-oxidative-stress-induced-aging-in-chorion-cells
#4
Liping Feng, Terrence K Allen, William P Marinello, Amy P Murtha
INTRODUCTION: Oxidative stress-mediated fetal membrane cell aging is activated prematurely in preterm premature rupture of membranes (PPROMs). The mechanism of this phenomenon is largely understudied. Progesterone receptor membrane component 1 (PGRMC1) has been recognized as a potential protective component for maintaining fetal membrane integrity and healthy pregnancies. We aimed to investigate the effects of oxidative stress (represented by hydrogen peroxide [H2 O2]) on fetal membrane and chorion cell senescence, p38 mitogen-activated protein kinase (MAPK) phosphorylation, and sirtuin 3 (SIRT3) and to examine the roles of PGRMC1 in these effects...
January 1, 2018: Reproductive Sciences
https://www.readbyqxmd.com/read/29783682/heat-shock-gene-inactivation-and-protein-aggregation-with-links-to-chronic-diseases
#5
Ian James Martins
The heat shock response involved in protein misfolding is linked to the formation of toxic immunogenic proteins with heat shock proteins (HSP) as regulators of amyloid beta aggregation. The defective amyloid beta trafficking between different intracellular compartments is now relevant to HSPs and autoimmunity. Overnutrition, temperature dysregulation, and stress repress the heat shock gene Sirtuin 1 with the induction of HSP regulated amyloid beta aggregation involved in the autoimmune response. Defective circadian rhythm alterations are connected to inactivation of the peripheral sink amyloid beta clearance pathway and related to insulin resistance, protein aggregation, and autoimmune disease in non-alcoholic fatty liver disease (NAFLD) and various neurodegenerative diseases such as Alzheimer's disease...
May 18, 2018: Diseases (Basel)
https://www.readbyqxmd.com/read/29782205/nad-repletion-produces-no-therapeutic-effect-in-mice-with-respiratory-chain-complex-iii-deficiency-and-chronic-energy-deprivation
#6
Janne Purhonen, Jayasimman Rajendran, Saara Tegelberg, Olli-Pekka Smolander, Eija Pirinen, Jukka Kallijärvi, Vineta Fellman
Biosynthetic precursors of NAD+ can replenish a decreased cellular NAD+ pool and, supposedly via sirtuin (SIRT) deacetylases, improve mitochondrial function. We found decreased hepatic NAD+ concentration and downregulated biosynthesis in Bcs1lp.S78G knock-in mice with respiratory chain complex III deficiency and mitochondrial hepatopathy. Aiming at ameliorating disease progression via NAD+ repletion and improved mitochondrial function, we fed these mice nicotinamide riboside (NR), a NAD+ precursor. A targeted metabolomics verified successful administration and suggested enhanced NAD+ biosynthesis in the treated mice, although hepatic NAD+ concentration was unchanged at the end point...
May 21, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/29779969/increased-malondialdehyde-vs-reduced-sirtuin-1-in-relation-with-adiposity-atherogenicity-and-hematological-indices-in-metabolic-syndrome-patients-with-and-without-prediabetes
#7
Samar Abu Rkhaya, Nailya Bulatova, Violet Kasabri, Randa Naffa, Reema Alquoqa
BACKGROUND: Sirtuin 1 (SIRT 1) and malondialdehyde (MDA) were implicated in metabolic syndrome (MetS) and type 2 diabetes mellitus (T2DM) pathophysiology. AIMS AND METHODS: This cross-sectional study aimed to investigate both SIRT 1 and MDA in 30 lean healthy control, 31 normoglycemic MetS subjects and 30 MetS-Pre/T2DM drug naïve. C orrelation studies were established for both biomarkers with adiposity indices [conicity index (CI), waist circumference (WC), weight-to-height (WHtR) ratio, weight-to-hip (WHR) ratio, hip circumference (HC), and body adiposity index (BAI)], hematological indices [red cell distribution width (RDW), mean platelet volume (MPV), platelet-to-lymphcyte ratio (PLR), neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR)] and atherogenicity indices (atherogenicity index of plasma (AIP = log10 TG/HDL-C ratio), TC/HDL-C and LDL-C/HDL-C ratios]...
May 15, 2018: Diabetes & Metabolic Syndrome
https://www.readbyqxmd.com/read/29777709/amelioration-of-myocardial-ischemia-reperfusion-injury-by-sirt4-involves-mitochondrial-protection-and-reduced-apoptosis
#8
Guangwei Zeng, Hui Liu, Haiyan Wang
Apoptosis and mitochondria dysfunction are key contributors to myocardial ischemia-reperfusion (MI-R) injury. SIRT4, a mitochondrial-localized sirtuin, controls cellular energy metabolism and stress response, and is abundantly present in the heart, however, its role in MI-R injury is not clear. In the current study, we demonstrate that SIRT4 is downregulated in cardiomyocytes both in vitro and in vivo models after MI-R. Functionally, SIRT4 overexpression decreases myocardial infarct size and serum creatine phosphokinase (CPK) level, and vice versa, SIRT4 depletion by siRNA increases myocardial infarct size and serum CPK level...
May 16, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29775898/particle-induced-sirt1-downregulation-promotes-osteoclastogenesis-and-osteolysis-through-er-stress-regulation
#9
Liang Zhang, Dongmei Bao, Peng Li, Zhidong Lu, Long Pang, Zhirong Chen, Haohui Guo, Zhihui Gao, Qunhua Jin
BACKGROUND: Sirtuin 1 (SIRT1) downregulation has been found to be induced by wear particles in aseptic prosthesis loosening (APL). Osteoclastogenesis and osteoclast activation are the main pathological factors associated with APL. However, whether SIRT1 downregulation contributes to the formation and activation of osteoclasts through the induction of endoplasmic reticulum (ER) stress is unclear. METHODS: To address this, an osteolysis mouse model was used in which animals were treated with the SIRT1 activator, resveratrol (RES), or an ER stress inhibitor, 4-PBA, for two weeks...
May 15, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29774638/loss-of-sirtuin-1-and-mitofusin-2-contributes-to-enhanced-ischemia-reperfusion-injury-in-aged-livers
#10
Sung Kook Chun, Sooyeon Lee, Joseph Flores-Toro, Rebecca Y U, Ming-Jim Yang, Kristina L Go, Thomas G Biel, Catherine E Miney, Schiley Pierre Louis, Brian K Law, Mary E Law, Elizabeth M Thomas, Kevin E Behrns, Christiaan Leeuwenburgh, Jae-Sung Kim
Ischemia/reperfusion (I/R) injury is a causative factor contributing to morbidity and mortality during liver resection and transplantation. Livers from elderly patients have a poorer recovery from these surgeries, indicating reduced reparative capacity with aging. Mechanisms underlying this age-mediated hypersensitivity to I/R injury remain poorly understood. Here, we investigated how sirtuin 1 (SIRT1) and mitofusin 2 (MFN2) are affected by I/R in aged livers. Young (3 months) and old (23-26 months) male C57/BL6 mice were subjected to hepatic I/R in vivo...
May 17, 2018: Aging Cell
https://www.readbyqxmd.com/read/29774488/the-effect-of-oxygen-in-sirt3-mediated-myocardial-protection-a-proof-of-concept-study-in-cultured-cardiomyoblasts
#11
Philipp Diehl, Daniel S Gaul, Jonas Sogl, Ulrike Flierl, Darren Henstridge, Juergen Pahla, Heiko Bugger, Maximilian Y Emmert, Frank Ruschitzka, Christoph Bode, Thomas F Lüscher, Martin Moser, Christian M Matter, Karlheinz Peter, Stephan Winnik
Sirtuin 3 is a nicotinamide adenine dinucleotide dependent mitochondrial deacetylase that governs mitochondrial metabolism and oxidative defense. The demise in myocardial function following myocardial ischemia has been associated with mitochondrial dysfunction. Sirt3 maintains myocardial contractile function and protects from cardiac hypertrophy. The role of Sirt3 in ischemia is controversial. Our objective was to understand, under what circumstances Sirt3 is protective in different facets of ischemia, using an in vitro proof-of-concept approach based on simulated ischemia in cultured cardiomyoblasts...
May 17, 2018: Journal of Thrombosis and Thrombolysis
https://www.readbyqxmd.com/read/29769314/ablation-of-sirtuin5-in-the-postnatal-mouse-heart-results-in-protein-succinylation-and-normal-survival-in-response-to-chronic-pressure-overload
#12
Kathleen A Hershberger, Dennis M Abraham, Juan Liu, Jason W Locasale, Paul A Grimsrud, Matthew D Hirschey
Mitochondrial Sirtuin 5 (SIRT5) is an NAD+-dependent demalonylase, desuccinylase, and deglutarylase that controls several metabolic pathways. A number of recent studies point to SIRT5 desuccinylase activity being important in maintaining cardiac function and metabolism under stress. Previously, we described a phenotype of increased mortality in whole-body SIRT5KO mice exposed to chronic pressure overload compared to their littermate WT controls. To determine if the survival phenotype we reported was due to a cardiac-intrinsic or cardiac-extrinsic effect of SIRT5, we developed a tamoxifen-inducible, heart-specific SIRT5KO mouse model...
May 16, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29767533/sirt1-controls-poly-i-c-dependent-mmp9-activation-in-primary-human-nasal-epithelial-cells
#13
Masanobu Suzuki, Mahnaz Ramezanpour, Clare Cooksley, Jian Li, Yuji Nakamaru, Akihiro Homma, Alkis Psaltis, Peter-John Wormald, Sarah Vreugde
BACKGROUND: Matrix metalloproteinase 9 (MMP9) is thought to be involved in the etiopathogenesis of chronic rhinosinusitis with nasal polyps (CRSwNP) and cleaves collagen IV causing hyperpermeability of the basement membrane within mucosal tissue. It is known that MMP9 expression is negatively affected by sirtuin-1 (SIRT-1) in human monocytotic cells, retinal endothelial cells and epithelial carcinoma cells. However, it is unknown which factors affect MMP9 expression and activity in human nasal epithelial cells (HNECs)...
May 16, 2018: American Journal of Respiratory Cell and Molecular Biology
https://www.readbyqxmd.com/read/29764990/ire1%C3%AE-prevents-hepatic-steatosis-by-processing-and-promoting-the-degradation-of-select-micrornas
#14
Jie-Mei Wang, Yining Qiu, Zhao Yang, Hyunbae Kim, Qingwen Qian, Qinghua Sun, Chunbin Zhang, Lei Yin, Deyu Fang, Sung Hong Back, Randal J Kaufman, Ling Yang, Kezhong Zhang
Obesity or a high-fat diet represses the endoribonuclease activity of inositol-requiring enzyme 1α (IRE1α), a transducer of the unfolded protein response (UPR) in cells under endoplasmic reticulum (ER) stress. An impaired UPR is associated with hepatic steatosis and nonalcoholic fatty liver disease (NAFLD), which is caused by lipid accumulation in the liver. We found that IRE1α was critical to maintaining lipid homeostasis in the liver by repressing the biogenesis of microRNAs (miRNAs) that regulate lipid mobilization...
May 15, 2018: Science Signaling
https://www.readbyqxmd.com/read/29763382/kdm2b-is-a-histone-h3k79-demethylase-and-induces-transcriptional-repression-via-sirtuin-1-mediated-chromatin-silencing
#15
Joo-Young Kang, Ji-Young Kim, Kee-Beom Kim, Jin Woo Park, Hana Cho, Ja Young Hahm, Yun-Cheol Chae, Daehwan Kim, Hyun Kook, Sangmyeong Rhee, Nam-Chul Ha, Sang-Beom Seo
The methylation of histone H3 lysine 79 (H3K79) is an active chromatin marker and is prominent in actively transcribed regions of the genome; however, demethylase of H3K79 remains unknown despite intensive research. Here, we show that KDM2B, also known as FBXL10 and a member of the Jumonji C family of proteins known for its histone H3K36 demethylase activity, is a di- and trimethyl H3K79 demethylase. We demonstrate that KDM2B induces transcriptional repression of HOXA7 and MEIS1 via occupancy of promoters and demethylation of H3K79...
May 15, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/29760950/genipin-alleviates-vascular-hyperpermeability-following-hemorrhagic-shock-by-up-regulation-of-sirt3-autophagy
#16
Cai Shumin, Xu Wei, Li Yunfeng, Liang Jiangshui, Gao Youguang, Chen Zhongqing, Li Tao
Genipin (GP) is commonly used to treat cardiovascular diseases; however, the protective action of GP against vascular hyperpermeability (VH) has not been reported. We previously reported that intrinsic apoptotic signaling (IAS) is involved in VH following hemorrhagic shock (HS). GP inhibits apoptosis, but the specific mechanism remains unclear. In the present study, we observed that GP protects against HS-induced VH in vitro and in vivo. We report that this protective effect is related to the inhibition of IAS by up-regulation of autophagy via sirtuin 3 (SIRT3)...
2018: Cell Death Discovery
https://www.readbyqxmd.com/read/29760313/detection-of-sirtuin-1-protein-expression-in-peripheral-blood-leukocytes-in-dogs
#17
Kuniko Yoshimura, Aya Matsuu, Kai Sasaki, Yasuyuki Momoi
Sirtuin-1 (SIRT1) is a nicotinamide adenine dinucleotide (NAD+ )-dependent histone deacetylase with a large number of protein substrates. It has attracted a lot of attention in association with extending lifespan. The objective of this study was to enable the evaluation of SIRT1 expression in peripheral blood mononuclear cells (PBMCs) from dogs by flow cytometry. Three transcript variants were amplified from PBMCs by reverse transcription PCR and the nucleotide sequences were analyzed. On the basis deduced amino acid sequence, a monoclonal antibody against human SIRT1, 1F3, was selected to detect canine SIRT1...
May 11, 2018: Journal of Veterinary Medical Science
https://www.readbyqxmd.com/read/29756546/sinomenine-induces-g1-phase-cell-cycle-arrest-and-apoptosis-in-malignant-glioma-cells-via-downregulation-of-sirtuin-1-and-induction-of-p53-acetylation
#18
Xiaoyan He, Mayinur Maimaiti, Yan Jiao, Xuegang Meng, Hongyan Li
Sinomenine, a bioactive alkaloid isolated from the traditional Chinese herb Sinomenium acutum, possesses antiinflammatory, antinociceptive, antifibrotic, and antitumorigenic properties. In this work, we sought to explore the biological effects of sinomenine on glioma cells. It was found that sinomenine caused a concentration-dependent inhibition of viability in both U87 and U251 glioma cells. Sinomenine at 16 μmol/L caused 55% to 60% reduction in the proliferation of U87 and U251 cells. Moreover, sinomenine treatment induced a G0/G1 cell cycle arrest and apoptosis...
January 1, 2018: Technology in Cancer Research & Treatment
https://www.readbyqxmd.com/read/29755342/mitochondria-estrogen-and-female-brain-aging
#19
REVIEW
Imane Lejri, Amandine Grimm, Anne Eckert
Mitochondria play an essential role in the generation of steroid hormones including the female sex hormones. These hormones are, in turn, able to modulate mitochondrial activities. Mitochondria possess crucial roles in cell maintenance, survival and well-being, because they are the main source of energy as well as of reactive oxygen species (ROS) within the cell. The impairment of these important organelles is one of the central features of aging. In women's health, estrogen plays an important role during adulthood not only in the estrous cycle, but also in the brain via neuroprotective, neurotrophic and antioxidant modes of action...
2018: Frontiers in Aging Neuroscience
https://www.readbyqxmd.com/read/29753648/nicotinamide-phosphoribosyltransferase-regulates-cocaine-reward-through-sirtuin-1
#20
Jueying Kong, Changman Du, Linhong Jiang, Wei Jiang, Pengchi Deng, Xue Shao, Baolai Zhang, Yan Li, Ruiming Zhu, Qian Zhao, Dengqi Fu, Hui Gu, Li Luo, Hailei Long, Yinglan Zhao, Xiaobo Cen
Nicotinamide phosphoribosyltransferase (NAMPT), a rate-limiting enzyme in nicotinamide adenine dinucleotide (NAD) biosynthesis in mammals, converts nicotinamide into nicotinamide mononucleotide (NMN). NMN is subsequently converted to NAD, a component that is critical for cell energy metabolism and survival. Sirtuin 1 (SIRT1), an NAD-dependent histone deacetylase, plays an important role in mediating memory and synaptic plasticity. Here, we found that NAMPT was significantly upregulated in the ventral tegmental area (VTA) of cocaine-conditioned mice...
May 10, 2018: Experimental Neurology
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