keyword
MENU ▼
Read by QxMD icon Read
search

SIRT5

keyword
https://www.readbyqxmd.com/read/28891317/the-role-of-sirtuins-in-antioxidant-and-redox-signaling
#1
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/28857557/genetically-encoded-fluorescent-probe-for-detecting-sirtuins-in-living-cells
#2
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/28756638/structure-based-discovery-of-new-selective-small-molecule-sirtuin-5-inhibitors
#3
Sha Liu, Sen Ji, Zhu-Jun Yu, Hua-Li Wang, Xu Cheng, Wei-Jian Li, Li Jing, Yamei Yu, Qiang Chen, Ling-Ling Yang, Guo-Bo Li, Yong Wu
Human sirtuin 5 (SIRT5) is a protein deacylase regulating metabolic pathways and stress responses and is implicated in metabolism-related diseases. Small-molecule inhibitors for SIRT5 are sought as chemical tools and potential therapeutics. Herein, we proposed a customized virtual screening approach targeting catalytically important and unique residues Tyr102 and Arg105 of SIRT5. Of the 20 tested virtual screening hits, six compounds displayed marked inhibitory activities against SIRT5. For the hit compound 19, a series of newly synthesized (E)-2-cyano-N-phenyl-3-(5-phenylfuran-2-yl)acrylamide derivatives/analogues were carried out structure-activity relationship analyses, resulting in new more potent inhibitors, among which 37 displayed the most potent inhibition to SIRT5 with an IC50 value of 5...
July 30, 2017: Chemical Biology & Drug Design
https://www.readbyqxmd.com/read/28739840/mitochondrial-sirtuins-in-cardiometabolic-diseases
#4
REVIEW
Xiaoqiang Tang, Xiao-Feng Chen, Hou-Zao Chen, De-Pei Liu
Mitochondria are heterogeneous and essentially contribute to cellular functions and tissue homeostasis. Mitochondrial dysfunction compromises overall cell functioning, tissue damage, and diseases. The advances in mitochondrion biology increase our understanding of mitochondrial dynamics, bioenergetics, and redox homeostasis, and subsequently, their functions in tissue homeostasis and diseases, including cardiometabolic diseases (CMDs). The functions of mitochondria mainly rely on the enzymes in their matrix...
August 15, 2017: Clinical Science (1979-)
https://www.readbyqxmd.com/read/28707980/extranuclear-sirtuins-and-metabolic-stress
#5
Mahmoud-Sobhy Elkhwanky, Jukka Hakkola
SIGNIFICANCE: Extranuclear sirtuins in cytosol (SIRT2) and mitochondria (SIRT3, SIRT4, and SIRT5) are key regulators of metabolic enzymes and the antioxidative defense mechanisms. They play an important role in the adjustment of metabolic pathways in alterations of the nutritional status. Recent Advances: Recent studies have shown that in addition to lysine deacetylation, sirtuins catalyze several different lysine deacylation reactions, removal of lipid modifications, and adenosine diphosphate-ribosylation...
August 11, 2017: Antioxidants & Redox Signaling
https://www.readbyqxmd.com/read/28707979/emerging-roles-for-sirt5-in-metabolism-and-cancer
#6
Lauren Rose Bringman-Rodenbarger, Angela H Guo, Costas A Lyssiotis, David B Lombard
SIGNIFICANCE: Developing evidence in the literature suggests that SIRT5 may be involved in metabolic reprogramming, an emerging hallmark of cancer by which neoplastic cells reconfigure their metabolism to support the anabolic demands of rapid cell division. Sirtuin 5 (SIRT5) is one of the seven members of the nicotinamide adenine dinucleotide (NAD+)-dependent sirtuin family of lysine deacylases. It removes succinyl, malonyl, and glutaryl groups from protein targets within the mitochondrial matrix and other subcellular compartments...
July 14, 2017: Antioxidants & Redox Signaling
https://www.readbyqxmd.com/read/28631845/mild-metabolic-perturbations-alter-succinylation-of-mitochondrial-proteins
#7
Huanlian Chen, Hui Xu, Samuel Potash, Anatoly Starkov, Vsevolod V Belousov, Dmitry S Bilan, Travis T Denton, Gary E Gibson
Succinylation of proteins is widespread, modifies both the charge and size of the molecules, and can alter their function. For example, liver mitochondrial proteins have 1,190 unique succinylation sites representing multiple metabolic pathways. Succinylation is sensitive to both increases and decreases of the NAD(+) -dependent desuccinylase, SIRT5. Although the succinyl group for succinylation is derived from metabolism, the effects of systematic variation of metabolism on mitochondrial succinylation are not known...
November 2017: Journal of Neuroscience Research
https://www.readbyqxmd.com/read/28614718/sirt5-desuccinylates-and-activates-pyruvate-kinase-m2-to-block-macrophage-il-1%C3%AE-production-and-to-prevent-dss-induced-colitis-in-mice
#8
Fang Wang, Ke Wang, Wei Xu, Shimin Zhao, Dan Ye, Yi Wang, Ying Xu, Lisha Zhou, Yiwei Chu, Cuiping Zhang, Xue Qin, Pengyuan Yang, Hongxiu Yu
LPS-activated macrophages undergo a metabolic shift from dependence on mitochondria-produced ATP to reliance on aerobic glycolysis, where PKM2 is a critical determinant. Here, we show that PKM2 is a physiological substrate of SIRT5 and that SIRT5-regulated hypersuccinylation inhibits the pyruvate kinase activity of PKM2 by promoting its tetramer-to-dimer transition. Moreover, a succinylation-mimetic PKM2 K311E mutation promotes nuclear accumulation and increases protein kinase activity. Furthermore, we show that SIRT5-dependent succinylation promotes PKM2 entry into nucleus, where a complex of PKM2-HIF1α is formed at the promoter of IL-1β gene in LPS-stimulated macrophages...
June 13, 2017: Cell Reports
https://www.readbyqxmd.com/read/28559847/high-sensitivity-of-sirt3-deficient-hearts-to-ischemia-reperfusion-is-associated-with-mitochondrial-abnormalities
#9
Rebecca M Parodi-Rullán, Xavier Chapa-Dubocq, Pedro J Rullán, Sehwan Jang, Sabzali Javadov
Aim: Sirtuins are NAD(+)-dependent deacetylases that regulate cell metabolism through protein acetylation/deacetylation, and SIRT3 is the major deacetylase among mitochondrial isoforms. Here, we elucidated the possible role of acetylation of cyclophilin D, a key regulator of the mitochondrial permeability transition pore (mPTP), in mitochondria-mediated cardiac dysfunction induced by ischemia-reperfusion (IR) in wild type (WT) and SIRT3 knockout (SIRT3(-/-)) mice. Materials and Methods: Isolated and Langendorff-mode perfused hearts of WT and SIRT3(-/-) mice were subjected to 25-min global ischemia followed by 60-min of reperfusion in the presence or absence of the mPTP inhibitor, sanglifehrin A (SfA)...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28514599/a-bioenergetics-systems-evaluation-of-ketogenic-diet-liver-effects
#10
Lewis J Hutfles, Heather M Wilkins, Scott J Koppel, Ian W Weidling, J Eva Selfridge, Eephie Tan, John P Thyfault, Chad Slawson, Aron W Fenton, Hao Zhu, Russell H Swerdlow
Ketogenic diets induce hepatocyte fatty acid oxidation and ketone body production. To further evaluate how ketogenic diets affect hepatocyte bioenergetic infrastructure, we analyzed livers from C57Bl/6J male mice maintained for 1 month on a ketogenic or standard chow diet. Compared with the standard diet, the ketogenic diet increased cytosolic and mitochondrial protein acetylation and also altered protein succinylation patterns. SIRT3 protein decreased while SIRT5 protein increased, and gluconeogenesis, oxidative phosphorylation, and mitochondrial biogenesis pathway proteins were variably and likely strategically altered...
May 17, 2017: Applied Physiology, Nutrition, and Metabolism, Physiologie Appliquée, Nutrition et Métabolisme
https://www.readbyqxmd.com/read/28461090/nad-dependent-deacetylase-sirtuin-5-rescues-the-innate-inflammatory-response-of-endotoxin-tolerant-macrophages-by-promoting-acetylation-of-p65
#11
Kewei Qin, Chaofeng Han, Hua Zhang, Tianliang Li, Nan Li, Xuetao Cao
The induction and persistence of a hypo-inflammatory and immunosuppressive state in severe sepsis is commonly associated with increased risks of secondary infections and mortality. Toll-like receptor (TLR)-triggered inflammatory response of macrophages/monocytes plays an important role in determining the outcome of hyper-inflammation during the acute phase and the hypo-inflammation during immunosuppressive phase of sepsis. However, the mechanisms for controlling hypo-inflammatory response in endotoxin tolerant macrophages remain to be fully understood...
July 2017: Journal of Autoimmunity
https://www.readbyqxmd.com/read/28458255/lysine-desuccinylase-sirt5-binds-to-cardiolipin-and-regulates-the-electron-transport-chain
#12
Yuxun Zhang, Sivakama S Bharathi, Matthew J Rardin, Jie Lu, Katherine V Maringer, Sunder Sims-Lucas, Edward V Prochownik, Bradford W Gibson, Eric S Goetzman
SIRT5 is a lysine desuccinylase known to regulate mitochondrial fatty acid oxidation and the urea cycle. Here, SIRT5 was observed to bind to cardiolipin via an amphipathic helix on its N terminus. In vitro, succinyl-CoA was used to succinylate liver mitochondrial membrane proteins. SIRT5 largely reversed the succinyl-CoA-driven lysine succinylation. Quantitative mass spectrometry of SIRT5-treated membrane proteins pointed to the electron transport chain, particularly Complex I, as being highly targeted for desuccinylation by SIRT5...
June 16, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28340937/sirtuin-5-protects-mitochondria-from-fragmentation-and-degradation-during-starvation
#13
Hala Guedouari, Tanya Daigle, Luca Scorrano, Etienne Hebert-Chatelain
During starvation, intra-mitochondrial sirtuins, NAD(+) sensitive deacylating enzymes that modulate metabolic homeostasis and survival, directly adjust mitochondrial function to nutrient availability; concomitantly, mitochondria elongate to escape autophagic degradation. However, whether sirtuins also impinge on mitochondrial dynamics is still uncharacterized. Here we show that the mitochondrial Sirtuin 5 (Sirt5) is essential for starvation induced mitochondrial elongation. Deletion of Sirt5 in mouse embryonic fibroblasts increased levels of mitochondrial dynamics of 51kDa protein and mitochondrial fission protein 1, leading to mitochondrial accumulation of the pro-fission dynamin related protein 1 and to mitochondrial fragmentation...
January 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28050792/alpha-synuclein-alters-differently-gene-expression-of-sirts-parps-and-other-stress-response-proteins-implications-for-neurodegenerative-disorders
#14
J Motyl, P L Wencel, M Cieślik, R P Strosznajder, J B Strosznajder
Alpha-synuclein (ASN) is a presynaptic protein that can easily change its conformation under different types of stress. It's assumed that ASN plays an important role in the pathogenesis of Parkinson's and Alzheimer's disease. However, the molecular mechanism of ASN toxicity has not been elucidated. This study focused on the role of extracellular ASN (eASN) in regulation of transcription of sirtuins (Sirts) and DNA-bound poly(ADP-ribose) polymerases (PARPs) - proteins crucial for cells' survival/death. Our results indicate that eASN enhanced the free radicals level, decreased mitochondria membrane potential, cells viability and activated cells' death...
January 3, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28042700/a-versatile-approach-for-site-specific-lysine-acylation-in-proteins
#15
Zhipeng A Wang, Yadagiri Kurra, Xin Wang, Yu Zeng, Yan-Jiun Lee, Vangmayee Sharma, Hening Lin, Susie Y Dai, Wenshe R Liu
Using amber suppression in coordination with a mutant pyrrolysyl-tRNA synthetase-tRNA(Pyl) pair, azidonorleucine is genetically encoded in E. coli. Its genetic incorporation followed by traceless Staudinger ligation with a phosphinothioester allows the convenient synthesis of a protein with a site-specifically installed lysine acylation. By simply changing the phosphinothioester identity, any lysine acylation type could be introduced. Using this approach, we demonstrated that both lysine acetylation and lysine succinylation can be installed selectively in ubiquitin and synthesized histone H3 with succinylation at its K4 position (H3K4su)...
February 1, 2017: Angewandte Chemie
https://www.readbyqxmd.com/read/28036303/desuccinylation-of-pyruvate-kinase-m2-by-sirt5-contributes-to-antioxidant-response-and-tumor-growth
#16
Ye Xiangyun, Niu Xiaomin, Gu Linping, Xu Yunhua, Li Ziming, Yu Yongfeng, Chen Zhiwei, Lu Shun
Tumor cells trends to express high level of pyruvate kinase M2 (PKM2). The inhibition of PKM2 activity is needed for antioxidant response by diverting glucose flux into the pentose phosphate pathway and thus generating sufficient reducing potential. Here we report that PKM2 is succinylated at lysine 498 (K498) and succinylation increases its activity. SIRT5 binds to, desuccinylates and inhibits PKM2 activity. Increased level of reactive oxygen species (ROS) decreases both the succinylation and activity of PKM2 by increasing its binding to SIRT5...
January 24, 2017: Oncotarget
https://www.readbyqxmd.com/read/28004755/stat3-undergoes-acetylation-dependent-mitochondrial-translocation-to-regulate-pyruvate-metabolism
#17
Yan S Xu, Jinyuan J Liang, Yumei Wang, Xiang-Zhong J Zhao, Li Xu, Ye-Yang Xu, Quanli C Zou, Junxun M Zhang, Cheng-E Tu, Yan-Ge Cui, Wei-Hong Sun, Chao Huang, Jing-Hua Yang, Y Eugene Chin
Cytoplasmic STAT3, after activation by growth factors, translocates to different subcellular compartments, including nuclei and mitochondria, where it carries out different biological functions. However, the precise mechanism by which STAT3 undergoes mitochondrial translocation and subsequently regulates the tricarboxylic acid (TCA) cycle-electron transport chain (ETC) remains poorly understood. Here, we clarify this process by visualizing STAT3 acetylation in starved cells after serum reintroduction or insulin stimulation...
December 22, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27858336/sirtuin-5-a-review-of-structure-known-inhibitors-and-clues-for-developing-new-inhibitors
#18
REVIEW
Lingling Yang, Xiaobo Ma, Yanying He, Chen Yuan, Quanlong Chen, Guobo Li, Xianggui Chen
Sirtuins (SIRTs) are nicotinamide adenine dinucleotide (NAD+)-dependent protein deacetylases, which regulate important biological processes ranging from apoptosis, age-associated pathophysiologies, adipocyte and muscle differentiation, and energy expenditure to gluconeogenesis. Very recently, sirtuin 5 (SIRT5) has received considerable attention due to that it was found to have weak deacetylase activity but strong desuccinylase, demalonylase and deglutarylase activities, and it was also found to be associated with several human diseases such as cancer, Alzheimer's disease, and Parkinson's disease...
March 2017: Science China. Life Sciences
https://www.readbyqxmd.com/read/27763519/segmental-aging-underlies-the-development-of-a-parkinson-phenotype-in-the-as-agu-rat
#19
Sohair M Khojah, Anthony P Payne, Dagmara McGuinness, Paul G Shiels
There is a paucity of information on the molecular biology of aging processes in the brain. We have used biomarkers of aging (SA β-Gal, p16(Ink4a), Sirt5, Sirt6, and Sirt7) to demonstrate the presence of an accelerated aging phenotype across different brain regions in the AS/AGU rat, a spontaneous Parkinsonian mutant of PKCγ derived from a parental AS strain. P16(INK4a) expression was significantly higher in AS/AGU animals compared to age-matched AS controls (p < 0.001) and displayed segmental expression across various brain regions...
October 17, 2016: Cells
https://www.readbyqxmd.com/read/27686746/in-low-protein-diets-microrna-19b-regulates-urea-synthesis-by-targeting-sirt5
#20
Rui-Ping Sun, Qian-Yun Xi, Jia-Jie Sun, Xiao Cheng, Yan-Ling Zhu, Ding-Ze Ye, Ting Chen, Li-Min Wei, Rui-Song Ye, Qing-Yan Jiang, Yong-Liang Zhang
Ammonia detoxification, which takes place via the hepatic urea cycle, is essential for nitrogen homeostasis and physiological well-being. It has been reported that a reduction in dietary protein reduces urea nitrogen. MicroRNAs (miRNAs) are major regulatory non-coding RNAs that have significant effects on several metabolic pathways; however, little is known on whether miRNAs regulate hepatic urea synthesis. The objective of this study was to assess the miRNA expression profile in a low protein diet and identify miRNAs involved in the regulation of the hepatic urea cycle using a porcine model...
September 30, 2016: Scientific Reports
keyword
keyword
29429
1
2
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read
×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"