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https://www.readbyqxmd.com/read/28935506/endothelial-specific-sirt3-deletion-impairs-glycolysis-and-angiogenesis-and-causes-diastolic-dysfunction
#1
Xiaochen He, Heng Zeng, Sean T Chen, Richard J Roman, Judy L Aschner, Sean Didion, Jian-Xiong Chen
Endothelial glycolysis plays a critical role in the regulation of angiogenesis. We investigated the role of Sirtuin 3 (SIRT3) on endothelial cell (EC) glycolytic metabolism, angiogenesis, and diastolic function. Our aim was to test the hypothesis that loss of SIRT3 in ECs impairs endothelial glycolytic metabolism and angiogenesis and contributes to myocardial capillary rarefaction and the development of diastolic dysfunction. Using SIRT3 deficient ECs, SIRT3 was found to regulate a metabolic switch between mitochondrial respiration and glycolysis...
September 18, 2017: Journal of Molecular and Cellular Cardiology
https://www.readbyqxmd.com/read/28935184/differential-expression-of-the-sirtuin-family-in-renal-cell-carcinoma-aspects-of-carcinogenesis-and-prognostic-significance
#2
Seong Uk Jeh, Jung Je Park, Jong Sil Lee, Dong Chul Kim, Jungmo Do, Sin Woo Lee, See Min Choi, Jae Seog Hyun, Deok Ha Seo, Chunwoo Lee, Sung Chul Kam, Ky Hyun Chung, Jeong Seok Hwa
OBJECTIVES: Sirtuins (1-7) are evolutionarily conserved NAD-dependent deacetylases that play an important role in carcinogenesis. However, their role in renal cell carcinoma (RCC) remains unclear. The objective of the present study was to examine the role of SIRTs in RCC carcinogenesis and prognosis. MATERIALS AND METHODS: Paraffin-embedded specimens from 102 patients who underwent extirpative renal surgeries for renal masses between January 2004 and December 2010 were examined...
September 18, 2017: Urologic Oncology
https://www.readbyqxmd.com/read/28914882/sirt3-sod2-maintains-osteoblast-differentiation-and-bone-formation-by-regulating-mitochondrial-stress
#3
Jing Gao, Zhihui Feng, Xueqiang Wang, Mengqi Zeng, Jing Liu, Shujun Han, Jie Xu, Lei Chen, Ke Cao, Jiangang Long, Zongfang Li, Weili Shen, Jiankang Liu
Recent studies have revealed robust metabolic changes during cell differentiation. Mitochondria, the organelles where many vital metabolic reactions occur, may play an important role. Here, we report the involvement of SIRT3-regulated mitochondrial stress in osteoblast differentiation and bone formation. In both the osteoblast cell line MC3T3-E1 and primary calvarial osteoblasts, robust mitochondrial biogenesis and supercomplex formation were observed during differentiation, accompanied by increased ATP production and decreased mitochondrial stress...
September 15, 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/28912098/melatonin-mediated-upregulation-of-sirt3-attenuates-sodium-fluoride-induced-hepatotoxicity-by-activating-the-mt1-pi3k-akt-pgc-1%C3%AE-signaling-pathway
#4
Chao Song, Jiamin Zhao, Beibei Fu, Dan Li, Tingchao Mao, Wei Peng, Haibo Wu, Yong Zhang
Mitochondrial reactive oxygen species (ROS) production has been implicated in the pathogenesis of fluoride toxicity in liver. Melatonin, an indolamine synthesized in the pineal gland, was previously shown to protect against sodium fluoride (NaF)-induced hepatotoxicity. This study investigated the protective effects of melatonin pretreatment on NaF-induced hepatotoxicity and elucidates the potential mechanism of melatonin-mediated protection. Reducing mitochondrial ROS by melatonin substantially attenuated NaF-induced NADPH oxidase 4 (Nox4) upregulation and cytotoxicity in L-02 cells...
September 11, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28911171/sirtuin-3-promotes-adipogenesis-osteoclastogenesis-and-bone-loss-in-aging-male-mice
#5
Linh Ho, Liping Wang, Theresa M Roth, Yong Pan, Eric M Verdin, Edward C Hsiao, Robert A Nissenson
Sirtuin-3 (Sirt3) is an essential metabolic regulatory enzyme that plays an important role in mitochondrial metabolism, but its role in bone marrow and skeletal homeostasis remains largely unknown. In this study, we hypothesize that increased expression of Sirt3 plays a role in skeletal aging. Using mice that overexpress Sirt3 [i.e., Sirt3 transgenic (Sirt3Tg)], we show that Sirt3 is a positive regulator of adipogenesis and osteoclastogenesis and a negative regulator of skeletal homeostasis. Sirt3Tg mice exhibited more adipocytes in the tibia compared with control mice...
September 1, 2017: Endocrinology
https://www.readbyqxmd.com/read/28891317/the-role-of-sirtuins-in-antioxidant-and-redox-signaling
#6
Chandra K Singh, Gagan Chhabra, Mary Ndiaye, Liz Mariely Garcia-Peterson, Nicholas John Mack, Nihal Ahmad
SIGNIFICANCE: Antioxidant and redox signaling (ARS) events are regulated by critical molecules that modulate antioxidants, reactive oxygen or nitrogen species (ROS/RNS) and/or oxidative stress within the cell. Imbalances in these molecules can disturb cellular functions to become pathogenic. Sirtuins serve as important regulators of ARS in cells. Recent Advances: Sirtuins (SIRTs 1-7) are a family of nicotinamide adenine dinucleotide (NAD)-dependent histone deacetylases with the ability to deacetylate histone and non-histone targets...
September 11, 2017: Antioxidants & Redox Signaling
https://www.readbyqxmd.com/read/28882480/short-term-administration-of-nicotinamide-mononucleotide-preserves-cardiac-mitochondrial-homeostasis-and-prevents-heart-failure
#7
Rongli Zhang, Yuyan Shen, Lin Zhou, Panjamaporn Sangwung, Hisashi Fujioka, Lilei Zhang, Xudong Liao
Heart failure is associated with mitochondrial dysfunction so that restoring or improving mitochondrial health is of therapeutic importance. Recently, reduction in NAD(+) levels and NAD(+)-mediated deacetylase activity has been recognized as negative regulators of mitochondrial function. Using a cardiac specific KLF4 deficient mouse line that is sensitive to stress, we found mitochondrial protein hyperacetylation coupled with reduced Sirt3 and NAD(+) levels in the heart before stress, suggesting that the KLF4-deficient heart is predisposed to NAD(+)-associated defects...
September 5, 2017: Journal of Molecular and Cellular Cardiology
https://www.readbyqxmd.com/read/28878358/enoyl-coa-hydratase-1-regulates-mtor-signaling-and-apoptosis-by-sensing-nutrients
#8
Ya-Kun Zhang, Yuan-Yuan Qu, Yan Lin, Xiao-Hui Wu, Hou-Zao Chen, Xu Wang, Kai-Qiang Zhou, Yun Wei, Fushen Guo, Cui-Fang Yao, Xia-Di He, Li-Xia Liu, Chen Yang, Zong-Yuan Guan, Shi-Dong Wang, Jianyuan Zhao, De-Pei Liu, Shi-Min Zhao, Wei Xu
The oncogenic mechanisms of overnutrition, a confirmed independent cancer risk factor, remain poorly understood. Herein, we report that enoyl-CoA hydratase-1 (ECHS1), the enzyme involved in the oxidation of fatty acids (FAs) and branched-chain amino acids (BCAAs), senses nutrients and promotes mTOR activation and apoptotic resistance. Nutrients-promoted acetylation of lys(101) of ECHS1 impedes ECHS1 activity by impairing enoyl-CoA binding, promoting ECHS1 degradation and blocking its mitochondrial translocation through inducing ubiquitination...
September 6, 2017: Nature Communications
https://www.readbyqxmd.com/read/28871042/trimethylamine-n-oxide-induces-vascular-inflammation-by-activating-the-nlrp3-inflammasome-through-the-sirt3-sod2-mtros-signaling-pathway
#9
Ming-Liang Chen, Xiao-Hui Zhu, Li Ran, He-Dong Lang, Long Yi, Man-Tian Mi
BACKGROUND: Trimethylamine-N-oxide (TMAO) has recently been identified as a novel and independent risk factor for promoting atherosclerosis through inducing vascular inflammation. However, the exact mechanism is currently unclear. Studies have established a central role of nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome in the pathogenesis of vascular inflammation. Here, we examined the potential role of the NLRP3 inflammasome in TMAO-induced vascular inflammation in vitro and in vivo and the underlying mechanisms...
September 4, 2017: Journal of the American Heart Association
https://www.readbyqxmd.com/read/28870631/the-sirtuin-family-members-sirt1-sirt3-and-sirt6-their-role-in-vascular-biology-and-atherogenesis
#10
REVIEW
Bożena Sosnowska, Mohsen Mazidi, Peter Penson, Anna Gluba-Brzózka, Jacek Rysz, Maciej Banach
The sirtuins, silent mating-type information regulation 2 (SIRTs), are a family of nicotinamide adenine dinucleotide (NAD(+))-dependent histone deacetylases with important roles in regulating energy metabolism and senescence. Activation of SIRTs appears to have beneficial effects on lipid metabolism and antioxidants, prompting investigation of the roles of these proteins in atherogenesis. Although clinical data are currently limited, the availability and safety of SIRT activators such as metformin and resveratrol provide an excellent opportunity to conduct research to better understand the role of SIRTs in human atherosclerosis...
August 26, 2017: Atherosclerosis
https://www.readbyqxmd.com/read/28867609/ampk-attenuates-ventricular-remodeling-and-dysfunction-following-aortic-banding-in-mice-via-the-sirt3-oxidative-stress-pathway
#11
Yili Chen, Cong Chen, Bin Dong, Fuwei Xing, Huiling Huang, Fengjuan Yao, Yuedong Ma, Jiangui He, Yugang Dong
Although recent findings have suggested that AMP-activated protein kinase (AMPK) exerts inhibitory effects on cardiac remodeling secondary to hypertension, the mechanism and optimal duration of treatment remain unknown. Mice with descending aortic banding (AB) or subjected to sham operation received subcutaneous injection of either AICAR (0.5mg∙g(-1)∙day(-1)) or vehicle over 4 week periods. At the end of 4 week treatment, left ventricular (LV) remodeling and function were evaluated with histological analysis and echocardiography...
August 31, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28867266/low-sirt3-expression-contributes-to-tumor-progression-development-and-poor-prognosis-in-human-pancreatic-carcinoma
#12
Shanshan Huang, Xiong Chen, Jiawei Zheng, Yufang Huang, Li Song, Yin Yin, Jianping Xiong
SIRT3, an important mitochondrial protein, may act as either an oncogene or tumor suppressor depending on the tumor-type. The aim of this study was to investigate the expression of SIRT3 in pancreatic carcinoma (PC) and its clinical association in PC patients. Immunohistochemistry was adopted to investigate the expression of SIRT3 in cancer and corrresponding adjacent non-cancer tissues across 79 patients with PC. The log-rank test and Cox hazard model were used to estimate the relationship between SIRT3 expression and prognosis...
July 23, 2017: Pathology, Research and Practice
https://www.readbyqxmd.com/read/28862956/sirtuin-3-deficiency-accelerates-hypertensive-cardiac-remodeling-by-impairing-angiogenesis
#13
Tong Wei, Gaojian Huang, Jing Gao, Chenglin Huang, Mengwei Sun, Jian Wu, Juan Bu, Weili Shen
BACKGROUND: Emerging evidence indicates that impaired angiogenesis may contribute to hypertension-induced cardiac remodeling. The nicotinamide adenine dinucleotide-dependent deacetylase Sirtuin 3 (SIRT3) has the potential to modulate angiogenesis, but this has not been confirmed. As such, the aim of this study was to examine the relationship between SIRT3-mediated angiogenesis and cardiac remodeling. METHODS AND RESULTS: Our experiments were performed on SIRT3 knockout and age-matched wild-type mice infused with angiotensin II (1400 ng/kg per minute) or saline for 14 days...
August 19, 2017: Journal of the American Heart Association
https://www.readbyqxmd.com/read/28861173/therapeutic-effect-of-rosuvastatin-and-propylthiouracil-on-ameliorating-high-cholesterol-diet-induced-fatty-liver-disease-fibrosis-and-inflammation-in-rabbit
#14
Pao-Yuan Lin, Chih-Hung Chen, Christopher Glenn Wallace, Kuan-Hung Chen, Chia-Lo Chang, Hong-Hwa Chen, Pei-Hsun Sung, Kun-Chen Lin, Sheung-Fat Ko, Cheuk-Kwan Sun, Hsueh-Wen Chang, Pei-Lin Shao, Mel S Lee, Hon-Kan Yip
This study tested the hypothesis that high-cholesterol diet (HCD)-induced fatty liver disease could be ameliorated by rosuvastatin (Ros) and propylthiouracil (PTU) therapy. Thirty-two Zealand rabbits were equally divided into group 1 (sham-control), group 2 (HCD for 8 weeks), group 3 [HCD-Ros (20 mg/kg/day administration after 4-week HFD for 4 weeks)], group 4 [HCD-PTU (0.1% PTU in drinking water) with treatment course as group 3]. Liver weight, fibrosis, collagen deposition area, and serum levels of AST/ALT were highest in group 2, lowest in group 1, and significantly higher in group 4 than group 3 (all P<0...
2017: American Journal of Translational Research
https://www.readbyqxmd.com/read/28857557/genetically-encoded-fluorescent-probe-for-detecting-sirtuins-in-living-cells
#15
Weimin Xuan, Anzhi Yao, Peter G Schultz
Sirtuins are NAD(+) dependent protein deacetylases, which are involved in many biological processes. We now report a novel genetically encoded fluorescent probe (EGFP-K85AcK) that responds to sirtuins in living cells. The probe design exploits a lysyl residue in EGFP that is essential for chromophore maturation, and is also an efficient deacetylation substrate for sirtuins. Analysis of activity in Escherichia coli ΔcobB revealed that the probe can respond to various human sirtuins, including SIRT1, SIRT2, SIRT3 and SIRT5...
August 31, 2017: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/28852116/studies-on-the-regulatory-mechanism-of-isocitrate-dehydrogenase-2-using-acetylation-mimics
#16
Yuqun Xu, Lingwen Liu, Akira Nakamura, Shinichi Someya, Takuya Miyakawa, Masaru Tanokura
Mitochondrial isocitrate dehydrogenase 2 (IDH2) converts NADP(+) to NADPH and promotes regeneration of reduced glutathione (GSH) by supplying NADPH to glutathione reductase or thioredoxin reductase. We have previously shown that under calorie restriction, mitochondrial deacetylase Sirt3 deacetylates and activates IDH2, thereby regulating the mitochondrial glutathione antioxidant defense system in mice. To investigate the regulatory mechanism of mIDH2 (mouse mitochondrial IDH2), we used lysine-to-glutamine (KQ) mutants to mimic acetylated lysines and screened 15 KQ mutants...
August 29, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28822994/glucagon-like-peptide-1-receptor-agonist-stimulates-mitochondrial-bioenergetics-in-human-adipocytes
#17
Joanna Góralska, Agnieszka Śliwa, Anna Gruca, Urszula Raźny, Monika Chojnacka, Anna Polus, Bogdan Solnica, Małgorzata Malczewska-Malec
Glucagon-like peptide 1 receptor agonists (GLP-1RAs) are relatively new pharmacological agents used to normalize glucose level in type 2 diabetes. Recently, GLP-1RAs have been approved for the treatment of obesity to reduce body weight in non-diabetic patients. The extra-pancre-atic effects of GLP-1RAs, as well as their molecular mechanism of action, are still poorly understood. Thus this study was aimed to verify the hypothesis that the mechanism of action of the GLP-1RAs involves mitochondria and that GLP-1RAs administration can improve mitochondrial functions...
2017: Acta Biochimica Polonica
https://www.readbyqxmd.com/read/28814987/green-tea-polyphenols-ameliorate-the-early-renal-damage-induced-by-a-high-fat-diet-via-ketogenesis-sirt3-pathway
#18
Weijie Yi, Xiao Xie, Miying Du, Yongjun Bu, Nannan Wu, Hui Yang, Chong Tian, Fangyi Xu, Siyun Xiang, Piwei Zhang, Zhuo Chen, Xuezhi Zuo, Chenjiang Ying
SCOPE: Several reports in the literature have suggested the renoprotective effects of ketone bodies and green tea polyphenols (GTPs). Our previous study found that GTP consumption could elevate the renal expression of the ketogenic rate-limiting enzyme, which was decreased by a high-fat diet (HFD) in rats. Here, we investigated whether ketogenesis can mediate renoprotection by GTPs against an HFD. METHODS AND RESULTS: Wistar rats were fed a standard or HFD with or without GTPs for 18 weeks...
2017: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/28813682/circadian-and-feeding-rhythms-orchestrate-the-diurnal-liver-acetylome
#19
Daniel Mauvoisin, Florian Atger, Loïc Dayon, Antonio Núñez Galindo, Jingkui Wang, Eva Martin, Laetitia Da Silva, Ivan Montoliu, Sebastiano Collino, Francois-Pierre Martin, Joanna Ratajczak, Carles Cantó, Martin Kussmann, Felix Naef, Frédéric Gachon
Lysine acetylation is involved in various biological processes and is considered a key reversible post-translational modification in the regulation of gene expression, enzyme activity, and subcellular localization. This post-translational modification is therefore highly relevant in the context of circadian biology, but its characterization on the proteome-wide scale and its circadian clock dependence are still poorly described. Here, we provide a comprehensive and rhythmic acetylome map of the mouse liver...
August 15, 2017: Cell Reports
https://www.readbyqxmd.com/read/28808064/obesity-and-aging-diminish-sirt1-mediated-deacetylation-of-sirt3-leading-to-hyperacetylation-and-decreased-activity-and-stability-of-sirt3
#20
Sanghoon Kwon, Sunmi Seok, Peter Yau, Xiaoling Li, Byron Kemper, Jongsook Kim Kemper
Sirtuin 3 (SIRT3) deacetylates and regulates many mitochondrial proteins to maintain health, but its functions are depressed in aging and obesity. The best-studied sirtuin, SIRT1, counteracts aging- and obesity-related diseases by deacetylating many proteins, but whether SIRT1 has a role in deacetylating and altering the function of SIRT3 is unknown. Here we show that SIRT3 is reversibly acetylated in the mitochondria and unexpectedly is a target of SIRT1 deacetylation. SIRT3 is hyperacetylated in aged and obese mice, in which SIRT1 activity is low, and SIRT3 acetylation at K57 inhibits its deacetylase activity and promotes protein degradation...
August 14, 2017: Journal of Biological Chemistry
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