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https://www.readbyqxmd.com/read/29777709/amelioration-of-myocardial-ischemia-reperfusion-injury-by-sirt4-involves-mitochondrial-protection-and-reduced-apoptosis
#1
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/29721988/role-of-sirtuins-in-retinal-function-under-basal-conditions
#2
Jonathan B Lin, Shunsuke Kubota, Raul Mostoslavsky, Rajendra S Apte
Sirtuins are NAD+ -dependent enzymes that govern cellular homeostasis by regulating the acylation status of their diverse target proteins. We recently demonstrated that both rod and cone photoreceptors rely on NAMPT-mediated NAD+ biosynthesis to meet their energetic requirements. Moreover, we found that this NAD+ -dependent retinal homeostasis relies, in part, on maintenance of optimal activity of the mitochondrial sirtuins and of SIRT3 in particular. Nonetheless, it is unknown whether other sirtuin family members also play important roles in retinal homeostasis...
2018: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/29710384/resveratrol-prevents-the-development-of-hypertension-programmed-by-maternal-plus-post-weaning-high-fructose-consumption-through-modulation-of-oxidative-stress-nutrient-sensing-signals-and-gut-microbiota
#3
You-Lin Tain, Wei-Chia Lee, Kay L H Wu, Steve Leu, Julie Y H Chan
SCOPE: High-fructose (HF) intake, oxidative stress, nutrient-sensing signals, and gut microbiota dysbiosis are closely related to the development of hypertension. We investigated whether resveratrol can prevent hypertension induced by maternal plus post-weaning HF diets in adult offspring via the above-mentioned mechanisms. METHODS AND RESULTS: Female Sprague-Dawley rats received either a normal (ND) or 60% high-fructose (HF) diet during gestation and lactation...
April 30, 2018: Molecular Nutrition & Food Research
https://www.readbyqxmd.com/read/29593712/mitochondrial-sirtuin-4-resolves-immune-tolerance-in-monocytes-by-rebalancing-glycolysis-and-glucose-oxidation-homeostasis
#4
Jie Tao, Jingpu Zhang, Yun Ling, Charles E McCall, Tie Fu Liu
The goal of this investigation was to define the molecular mechanism underlying physiologic conversion of immune tolerance to resolution of the acute inflammatory response, which is unknown. An example of this knowledge gap and its clinical importance is the broad-based energy deficit and immunometabolic paralysis in blood monocytes from non-survivors of human and mouse sepsis that precludes sepsis resolution. This immunometabolic dysregulation is biomarked by ex vivo endotoxin tolerance to increased glycolysis and TNF-α expression...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29571013/a-ternary-complex-model-of-sirtuin4-nad-glutamate-dehydrogenase
#5
Yusuke Kato, Hiroshi Kihara, Kiyoshi Fukui, Masaki Kojima
Sirtuin4 (Sirt4) is one of the mammalian homologues of Silent information regulator 2 (Sir2), which promotes the longevity of yeast, C. elegans, fruit flies and mice. Sirt4 is localized in the mitochondria, where it contributes to preventing the development of cancers and ischemic heart disease through regulating energy metabolism. The ADP-ribosylation of glutamate dehydrogenase (GDH), which is catalyzed by Sirt4, downregulates the TCA cycle. However, this reaction mechanism is obscure, because the structure of Sirt4 is unknown...
March 10, 2018: Computational Biology and Chemistry
https://www.readbyqxmd.com/read/29564694/differential-gene-expression-of-sirtuins-between-somatotropinomas-and-nonfunctioning-pituitary-adenomas
#6
Isabella P P Grande, Paulo V G H Amorim, Ane Caroline Thé B Freire, Raquel S Jallad, Nina R Musolino, Valter A Cescato, Gilberto O da Silva, Marcello D Bronstein, Ericka B Trarbach
Sirtuins 1-7 (SIRT) are a highly conserved family of histone deacetylases involved in the regulation of longevity that have a considerable impact in transcription, DNA repair regulation, telomeric stability, cell senescence and apoptosis. In the present study, SIRT1-7 mRNA levels were evaluated in 37 somatotropinomas and 31 nonfunctioning pituitary adenomas (NFPAs) using qPCR and relation to tumor size, invasiveness and Ki-67 proliferative index was made. Overexpression of SIRT1 was observed in 86.5% of somatotropinomas versus 41...
March 21, 2018: Pituitary
https://www.readbyqxmd.com/read/29557214/current-understanding-and-future-perspectives-of-the-roles-of-sirtuins-in-the-reprogramming-and-differentiation-of-pluripotent-stem-cells
#7
Yi-Chao Hsu, Yu-Ting Wu, Chia-Ling Tsai, Yau-Huei Wei
In mammalian cells, there are seven members of the sirtuin protein family (SIRT1-7). SIRT1, SIRT6, and SIRT7 catalyze posttranslational modification of proteins in the nucleus, SIRT3, SIRT4, and SIRT5 are in the mitochondria and SIRT2 is in the cytosol. SIRT1 can deacetylate the transcription factor SOX2 and regulate induced pluripotent stem cells (iPSCs) reprogramming through the miR-34a-SIRT1-p53 axis. SIRT2 can regulate the function of pluripotent stem cells through GSK3β. SIRT3 can positively regulate PPAR gamma coactivator 1-alpha (PGC-1α) expression during the differentiation of stem cells...
March 2018: Experimental Biology and Medicine
https://www.readbyqxmd.com/read/29540733/molecular-link-between-glucose-and-glutamine-consumption-in-cancer-cells-mediated-by-ctbp-and-sirt4
#8
Li Wang, Jing-Jing Li, Li-Yu Guo, Peipei Li, Zhiqiang Zhao, Haisheng Zhou, Li-Jun Di
Glucose and Glutamine are two essential ingredients for cell growth. However, it remains open for investigation whether there is a general mechanism that coordinates the consumption of glucose and glutamine in cancer cells. Glutamine is mainly metabolized through the glutaminolysis pathway and our previous report indicated that CtBP increases GDH activity and promotes glutaminolysis through repressing the expression of SIRT4, a well-known mitochondrion-located factor that inhibits glutaminolysis pathway. CtBP is known to be a sensor of intracellular metabolic status; we thus hypothesized that a consensus CtBP-SIRT4-GDH axis may mediate the crosstalk between glycolysis and glutaminolysis...
March 13, 2018: Oncogenesis
https://www.readbyqxmd.com/read/29514063/the-mitochondrial-acylome-emerges-proteomics-regulation-by-sirtuins-and-metabolic-and-disease-implications
#9
REVIEW
Chris Carrico, Jesse G Meyer, Wenjuan He, Brad W Gibson, Eric Verdin
Post-translational modification of lysine residues via reversible acylation occurs on proteins from diverse pathways, functions, and organisms. While nuclear protein acylation reflects the competing activities of enzymatic acyltransferases and deacylases, mitochondrial acylation appears to be driven mostly via a non-enzymatic mechanism. Three protein deacylases, SIRT3, SIRT4, and SIRT5, reside in the mitochondria and remove these modifications from targeted proteins in an NAD+ -dependent manner. Recent proteomic surveys of mitochondrial protein acylation have identified the sites of protein acetylation, succinylation, glutarylation, and malonylation and their regulation by SIRT3 and SIRT5...
March 6, 2018: Cell Metabolism
https://www.readbyqxmd.com/read/29413176/mammalian-sirtuins-sirt4-and-sirt7
#10
Shengchao Li, Weiping Zheng
Sirtuins are a family of intracellular enzymes whose enzymatic activities include catalyzing the β-nicotinamide adenine dinucleotide (β-NAD+ )-dependent Nɛ -acyl-lysine deacylation and the β-NAD+ -dependent mono-ADP-ribosylation. Among the seven sirtuin family members (i.e., SIRT1-7) thus far identified in mammals including humans, we know SIRT1/2/3/5/6 better than SIRT4/7 as for their enzymatic activities and the cellular roles of the reactions they catalyze. This chapter will provide an updated account on the enzymology and biology of SIRT4 and SIRT7, the two less well-understood mammalian sirtuins...
2018: Progress in Molecular Biology and Translational Science
https://www.readbyqxmd.com/read/29378963/sirt4-is-a-mitochondrial-regulator-of-metabolism-and-lifespan-in-drosophila-melanogaster
#11
Jason G Wood, Bjoern Schwer, Priyan C Wickremesinghe, Davis A Hartnett, Lucas Burhenn, Meyrolin Garcia, Michael Li, Eric Verdin, Stephen L Helfand
Sirtuins are an evolutionarily conserved family of NAD+ -dependent deacylases that control metabolism, stress response, genomic stability, and longevity. Here, we show the sole mitochondrial sirtuin in Drosophila melanogaster , Sirt4, regulates energy homeostasis and longevity. Sirt4 knockout flies have a short lifespan, with increased sensitivity to starvation and decreased fertility and activity. In contrast, flies overexpressing Sirt4 either ubiquitously or specifically in the fat body are long-lived. Despite rapid starvation, Sirt4 knockout flies paradoxically maintain elevated levels of energy reserves, including lipids, glycogen, and trehalose, while fasting, suggesting an inability to properly catabolize stored energy...
February 13, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29315230/maternal-high-fructose-intake-increases-the-vulnerability-to-post-weaning-high-fat-diet-induced-programmed-hypertension-in-male-offspring
#12
You-Lin Tain, Wei-Chia Lee, Kay L H Wu, Steve Leu, Julie Y H Chan
Widespread consumption of high-fructose and high-fat diets relates to the global epidemic of hypertension. Hypertension may originate from early life by a combination of prenatal and postnatal nutritional insults. We examined whether maternal high-fructose diet increases vulnerability to post-weaning high-fructose or high-fat diets induced hypertension in adult offspring and determined the underlying mechanisms. Pregnant Sprague-Dawley rats received regular chow (ND) or chow supplemented with 60% fructose (HFR) during the entire pregnancy and lactation periods...
January 9, 2018: Nutrients
https://www.readbyqxmd.com/read/29295643/the-genomic-landscape-of-two-burkitt-lymphoma-cases-and-derived-cell-lines-comparison-between-primary-and-relapse-samples
#13
Claudia M Wever, Dominique Geoffrion, Bruno M Grande, Stephen Yu, Miguel Alcaide, Maryse Lemaire, Yasser Riazalhosseini, Josée Hébert, Christina Gavino, Donald C Vinh, Tina Petrogiannis-Haliotis, Svetlana Dmitrienko, Koren K Mann, Ryan D Morin, Nathalie A Johnson
Relapse occurs in 10-40% of Burkitt lymphoma (BL) patients that have completed intensive chemotherapy regimens and is typically fatal. While treatment-naive BL has been characterized, the genomic landscape of BL at the time of relapse (rBL) has never been reported. Here, we present a genomic characterization of two rBL patients. The diagnostic samples had mutations common in BL, including MYC and CCND3. Additional mutations were detected at relapse, affecting important pathways such as NFκB (IKBKB) and MEK/ERK (NRAS) signaling, glutamine metabolism (SIRT4), and RNA processing (ZFP36L2)...
January 3, 2018: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/29261224/mitochondrial-sirtuins-in-the-rat-adrenal-gland-location-within-the-glands-of-males-and-females-hormonal-and-developmental-regulation-of-gene-expressions
#14
Piotr Celichowski, Karol Jopek, Marta Szyszka, Marianna Tyczewska, Ludwik K Malendowicz, Marcin Rucinski
INTRODUCTION: Sirtuins are NAD dependent class III histone deacetylases. In adrenal cortex mitochondria are able to transform - via nicotinamide nucleotide transhydrogenase (NNT) - NAD into NADPH, which is required for steroidogenesis. These findings suggest that sirtuins expressed in mitochondria, Sirt3, Sirt4 and Sirt5, may be associated with adrenal steroidogenesis. Therefore, the purpose of this study was to characterize the expression of mitochondrial sirtuins (Sirt3-5) in individual compartments of rat adrenal cortex, their developmental regulation and to demonstrate whether their expression is dependent on adrenocorticotrophic hormone (ACTH) and Nampt (nicotinamide phosphoribosyltransferase also known as visfatin/PBEF), the rate-limiting enzyme in the regulation of mammalian NAD synthesis...
2017: Folia Histochemica et Cytobiologica
https://www.readbyqxmd.com/read/29138502/crystal-structures-of-the-mitochondrial-deacylase-sirtuin-4-reveal-isoform-specific-acyl-recognition-and-regulation-features
#15
Martin Pannek, Zeljko Simic, Matthew Fuszard, Marat Meleshin, Dante Rotili, Antonello Mai, Mike Schutkowski, Clemens Steegborn
Sirtuins are evolutionary conserved NAD+ -dependent protein lysine deacylases. The seven human isoforms, Sirt1-7, regulate metabolism and stress responses and are considered therapeutic targets for aging-related diseases. Sirt4 locates to mitochondria and regulates fatty acid metabolism and apoptosis. In contrast to the mitochondrial deacetylase Sirt3 and desuccinylase Sirt5, no prominent deacylase activity and structural information are available for Sirt4. Here we describe acyl substrates and crystal structures for Sirt4...
November 15, 2017: Nature Communications
https://www.readbyqxmd.com/read/29081403/sirt4-interacts-with-opa1-and-regulates-mitochondrial-quality-control-and-mitophagy
#16
Alexander Lang, Ruchika Anand, Simone Altinoluk-Hambüchen, Hakima Ezzahoini, Anja Stefanski, Afshin Iram, Laura Bergmann, Jennifer Urbach, Philip Böhler, Jan Hänsel, Manuel Franke, Kai Stühler, Jean Krutmann, Jürgen Scheller, Björn Stork, Andreas S Reichert, Roland P Piekorz
The stress-responsive mitochondrial sirtuin SIRT4 controls cellular energy metabolism in a NAD+ -dependent manner and is implicated in cellular senescence and aging. Here we reveal a novel function of SIRT4 in mitochondrial morphology/quality control and regulation of mitophagy. We report that moderate overexpression of SIRT4, but not its enzymatically inactive mutant H161Y, sensitized cells to mitochondrial stress. CCCP-triggered dissipation of the mitochondrial membrane potential resulted in increased mitochondrial ROS levels and autophagic flux, but surprisingly led to increased mitochondrial mass and decreased Parkin-regulated mitophagy...
October 29, 2017: Aging
https://www.readbyqxmd.com/read/29059204/alterations-of-sirtuins-in-mitochondrial-cytochrome-c-oxidase-deficiency
#17
Arne Björn Potthast, Theresa Heuer, Simone Johanna Warneke, Anibh Martin Das
BACKGROUND: Sirtuins are NAD+ dependent deacetylases, which regulate mitochondrial energy metabolism as well as cellular response to stress. The NAD/NADH-system plays a crucial role in oxidative phosphorylation linking sirtuins and the mitochondrial respiratory chain. Furthermore, sirtuins are able to directly deacetylate and activate different complexes of the respiratory chain. This prompted us to analyse sirtuin levels in skin fibroblasts from patients with cytochrome c-oxidase (COX) deficiency and to test the impact of different pharmaceutical activators of sirtuins (SRT1720, paeonol) to modulate sirtuins and possibly respiratory chain enzymes in patient cells in vitro...
2017: PloS One
https://www.readbyqxmd.com/read/28891317/the-role-of-sirtuins-in-antioxidant-and-redox-signaling
#18
Chandra K Singh, Gagan Chhabra, Mary Ann Ndiaye, Liz Mariely Garcia-Peterson, Nicholas J Mack, Nihal Ahmad
SIGNIFICANCE: Antioxidant and redox signaling (ARS) events are regulated by critical molecules that modulate antioxidants, reactive oxygen species (ROS) or reactive nitrogen species (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 nonhistone targets...
March 10, 2018: Antioxidants & Redox Signaling
https://www.readbyqxmd.com/read/28820880/knock-out-of-a-mitochondrial-sirtuin-protects-neurons-from-degeneration-in-caenorhabditis-elegans
#19
Rachele Sangaletti, Massimo D'Amico, Jeff Grant, David Della-Morte, Laura Bianchi
Sirtuins are NAD⁺-dependent deacetylases, lipoamidases, and ADP-ribosyltransferases that link cellular metabolism to multiple intracellular pathways that influence processes as diverse as cell survival, longevity, and cancer growth. Sirtuins influence the extent of neuronal death in stroke. However, different sirtuins appear to have opposite roles in neuronal protection. In Caenorhabditis elegans, we found that knock-out of mitochondrial sirtuin sir-2.3, homologous to mammalian SIRT4, is protective in both chemical ischemia and hyperactive channel induced necrosis...
August 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28768896/the-effects-of-graded-levels-of-calorie-restriction-xi-evaluation-of-the-main-hypotheses-underpinning-the-life-extension-effects-of-cr-using-the-hepatic-transcriptome
#20
Davina Derous, Sharon E Mitchell, Lu Wang, Cara L Green, Yingchun Wang, Luonan Chen, Jing-Dong J Han, Daniel E L Promislow, David Lusseau, Alex Douglas, John R Speakman
Calorie restriction (CR) may extend longevity by modulating the mechanisms involved in aging. Different hypotheses have been proposed for its main mode of action. We quantified hepatic transcripts of male C57BL/6 mice exposed to graded levels of CR (0% to 40% CR) for three months, and evaluated the responses relative to these various hypotheses. Of the four main signaling pathways implied to be linked to the impact of CR on lifespan (insulin/insulin like growth factor 1 (IGF-1), nuclear factor-kappa beta (NF-ĸB), mechanistic target of rapamycin (mTOR) and sirtuins (SIRTs)), all the pathways except SIRT were altered in a manner consistent with increased lifespan...
July 31, 2017: Aging
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