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https://www.readbyqxmd.com/read/28813682/circadian-and-feeding-rhythms-orchestrate-the-diurnal-liver-acetylome
#1
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
#2
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
https://www.readbyqxmd.com/read/28805748/synthesis-and-evaluation-of-novel-benzofuran-derivatives-as-selective-sirt2-inhibitors
#3
Yumei Zhou, Huaqing Cui, Xiaoming Yu, Tao Peng, Gang Wang, Xiaoxue Wen, Yunbo Sun, Shuchen Liu, Shouguo Zhang, Liming Hu, Lin Wang
A series of benzofuran derivatives were designed and synthesized, and their inhibitory activites were measured against the SIRT1-3. The enzymatic assay showed that all the compounds showed certain anti-SIRT2 activity and selective over SIRT1 and SIRT3 with IC50 (half maximal inhibitory concentration) values at the micromolar level. The preliminary structure-activity relationships were analyzed and the binding features of compound 7e (IC50 3.81 µM) was predicted using the CDOCKER program. The results of this research could provide informative guidance for further optimizing benzofuran derivatives as potent SIRT2 inhibitors...
August 14, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28804553/sirt3-attenuates-doxorubicin-induced-cardiac-hypertrophy-and-mitochondrial-dysfunction-via-suppression-of-bnip3
#4
Qiong Du, Bin Zhu, Qing Zhai, Bo Yu
Doxorubicin (Dox) is an anthracycline antibiotic widely used in cancer treatment. Although its antitumor efficacy appears to be dose dependent, its clinical use is greatly restricted by development of cardiotoxicity. Sirtuin-3 (Sirt3) is the major deacetylase within the mitochondrial matrix that plays an important role in regulation of cardiac function. This study was performed to identify the regulatory role of Sirt3 on Dox-induced cardiac hypertrophy and mitochondrial dysfunction in rats in vivo and in vitro...
2017: American Journal of Translational Research
https://www.readbyqxmd.com/read/28804544/sirt3-attenuates-angii-induced-cardiac-fibrosis-by-inhibiting-myofibroblasts-transdifferentiation-via-stat3-nfatc2-pathway
#5
Xiaobin Guo, Fangying Yan, Jingyuan Li, Chunmei Zhang, Peili Bu
Cardiac fibrosis is a maladaptive response to various stresses, characterized by increased interstitial collagen deposition and progressive cardiac dysfunction. The transdifferentiation of fibroblasts into myofibroblasts is an essential process in the pathogenesis of cardiac fibrosis. SIRT3, as a mitochondrial NAD(+)-dependent histone deacetylase, has been demonstrated beneficial in many cardiovascular diseases. However, the specific mechanism of its protective role in cardiac fibrosis needs to be elucidated further...
2017: American Journal of Translational Research
https://www.readbyqxmd.com/read/28799020/from-discovery-of-the-chop-axis-and-targeting-clpp-to-the-identification-of-additional-axes-of-the-uprmt-driven-by-the-estrogen-receptor-and-sirt3
#6
Timothy C Kenny, Doris Germain
The mitochondrial UPR (UPR(mt)) is rapidly gaining attention. While most studies on the UPR(mt) have focused on its role in aging, emerging studies suggest an important role of the UPR(mt) in cancer. Further, several of the players of the UPR(mt) in mammalian cells have well reported roles in the maintenance of the organelle. The goal of this review is to emphasize aspects of the UPR(mt) that have been overlooked in the current literature, describe the role of specific players of the UPR(mt) in the biology of the mitochondria and highlight the intriguing possibility that targeting the UPR(mt) in cancer may be already within reach...
August 10, 2017: Journal of Bioenergetics and Biomembranes
https://www.readbyqxmd.com/read/28789977/ablation-of-systemic-sirt1-activity-promotes-nonalcoholic-fatty-liver-disease-by-affecting-liver-mesenteric-adipose-tissue-fatty-acid-mobilization
#7
Junrui Cheng, Chun Liu, Kangquan Hu, Andrew Greenberg, Dayong Wu, Lynne M Ausman, Michael W McBurney, Xiang-Dong Wang
Sirtuin 1 (SIRT1) has been reported to protect against nonalcoholic fatty liver disease (NAFLD) development. The mechanism of how SIRT1 deacetylase activity affects NAFLD has not been well investigated. The current investigation addressed the causal effect of systemic SIRT1 activity on NAFLD development and the underlying mechanism involved in both liver and mesenteric adipose tissue (MAT). Both SIRT1 homozygous mice ablated the catalytic activity (sirt1(Y/Y)) and their corresponding wild type littermates (WT) were fed a high fat diet (HFD, 60% calories from fat) for 34weeks...
August 5, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28763300/ablation-of-adipose-ho-1-expression-increases-white-fat-over-beige-fat-through-inhibition-of-mitochondrial-fusion-and-of-pgc1%C3%AE-in-female-mice
#8
Shailendra P Singh, Ilana Grant, Aliza Meissner, Attallah Kappas, Nader G Abraham
Background Hmox1 plays an important role in the regulation of mitochondrial bioenergetics and function by regulating cellular heme-derived CO and bilirubin. Previous studies have demonstrated that global disruption of HO-1 in humans and mice resulted in severe organ dysfunction. Methods We investigated the potential role of adipose-specific-HO-1 genetic ablation on adipose tissue function, mitochondrial quality control and energy expenditure by generating an adipo-HO-1 knockout mouse model (Adipo-HO-1-/-) and, in vitro, adipocyte cells in which HO activity was inhibited...
August 1, 2017: Hormone Molecular Biology and Clinical Investigation
https://www.readbyqxmd.com/read/28760703/berberine-induced-cardioprotection-and-sirt3-modulation-in-doxorubicin-treated-h9c2-cardiomyoblasts
#9
Ana R Coelho, Tatiana R Martins, Renata Couto, Cláudia Deus, Cláudia V Pereira, Rui F Simões, Albert A Rizvanov, Filomena Silva, Teresa Cunha-Oliveira, Paulo J Oliveira, Teresa L Serafim
Doxorubicin (DOX) is one of the most widely used anti-neoplastic agents. However, treatment with DOX is associated with cumulative cardiotoxicity inducing progressive cardiomyocyte death. Sirtuin 3 (Sirt3), a mitochondrial deacetylase, regulates the activity of proteins involved in apoptosis, autophagy and metabolism. Our hypothesis is that pharmacological modulation by berberine (BER) pre-conditioning of Sirt3 protein levels decreases DOX-induced cardiotoxicity. Our results showed that DOX induces cell death in all experimental groups...
July 28, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28760678/sirt3-inhibits-ang-ii-induced-transdifferentiation-of-cardiac-fibroblasts-through-%C3%AE-catenin-ppar-%C3%AE-signaling
#10
Fangying Yan, Xiaobin Guo, Xiaolan Shan, Jingyuan Li, Yi Yang, Jie Zhang, Xuefang Yan, Peili Bu
AIMS: Cardiac fibrosis is an inevitable process of numerous cardiovascular diseases in which the transdifferentiation of cardiac fibroblasts plays a pivotal role. Sirtuin3 (SIRT3) has been believed to protect against cardiac fibrosis. However, the mechanism underlying this beneficial effect has not yet been elucidated. In this study, we investigated the potential mechanism of SIRT3 on the inhibition of fibroblast-to-myoblast transdifferentiation. MAIN METHODS: Cells were stimulated by angiotension II (Ang II) with SIRT3 overexpression or knockdown...
July 28, 2017: Life Sciences
https://www.readbyqxmd.com/read/28752710/-nicotinamide-regulates-blood-glucose-level-and-affects-mitochondrial-superoxide-level-in-gestational-diabetic-rats
#11
Wang Li, Wang Yu, W U Haiying
Objective: To investigate the effects of nicotinamide (NAM) on blood glucose level and anti-oxidative enzyme activity in gestational diabetic (GDM) rats. Methods: GDM model was induced by injection of STZ (35 mg/kg) in pregnant female Sprague-Dawley rats. Nicotinamide was given to GDM rats by gavage at 50, 100 or 200 mg/kg q.d from gestational d 6 to d 20. The rats were divided into normal control group, GDM group (0 mg/kg), low-dose NAM group (50 mg/kg), middle-dose NAM group (100 mg/kg) and high-dose NAM group (200 mg/kg) with 8 animals in each group...
March 25, 2017: Zhejiang da Xue Xue Bao. Yi Xue Ban, Journal of Zhejiang University. Medical Sciences
https://www.readbyqxmd.com/read/28739840/mitochondrial-sirtuins-in-cardiometabolic-diseases
#12
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/28737710/cytoprotective-effect-of-the-ucp2-sirt3-signaling-pathway-by-decreasing-mitochondrial-oxidative-stress-on-cerebral-ischemia-reperfusion-injury
#13
REVIEW
Jing Su, Jie Liu, Xiao-Yu Yan, Yong Zhang, Juan-Juan Zhang, Li-Chao Zhang, Lian-Kun Sun
Recovered blood supply after cerebral ischemia for a certain period of time fails to restore brain function, with more severe dysfunctional problems developing, called cerebral ischemia-reperfusion injury (CIR). CIR involves several extremely complex pathophysiological processes in which the interactions between key factors at various stages have not been fully elucidated. Mitochondrial dysfunction is one of the most important mechanisms of CIR. The mitochondrial deacetylase, sirtuin 3 (SIRT3), can inhibit mitochondrial oxidative stress by deacetylation, to maintain mitochondrial stability...
July 24, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28724806/nicotinamide-mononucleotide-requires-sirt3-to-improve-cardiac-function-and-bioenergetics-in-a-friedreich-s-ataxia-cardiomyopathy-model
#14
Angelical S Martin, Dennis M Abraham, Kathleen A Hershberger, Dhaval P Bhatt, Lan Mao, Huaxia Cui, Juan Liu, Xiaojing Liu, Michael J Muehlbauer, Paul A Grimsrud, Jason W Locasale, R Mark Payne, Matthew D Hirschey
Increasing NAD+ levels by supplementing with the precursor nicotinamide mononucleotide (NMN) improves cardiac function in multiple mouse models of disease. While NMN influences several aspects of mitochondrial metabolism, the molecular mechanisms by which increased NAD+ enhances cardiac function are poorly understood. A putative mechanism of NAD+ therapeutic action exists via activation of the mitochondrial NAD+-dependent protein deacetylase sirtuin 3 (SIRT3). We assessed the therapeutic efficacy of NMN and the role of SIRT3 in the Friedreich's ataxia cardiomyopathy mouse model (FXN-KO)...
July 20, 2017: JCI Insight
https://www.readbyqxmd.com/read/28717408/sirt3-enhances-mesenchymal-stem-cell-longevity-and-differentiation
#15
Ryan A Denu
Mesenchymal stem cells (MSCs) are multipotent cells that are currently being investigated in a wide variety of clinical trials for their anti-inflammatory and immunomodulatory properties as well as their osteogenic and chondrogenic capabilities. However, there are considerable interdonor variability and heterogeneity of MSC populations, making it challenging to compare different products. Furthermore, proliferation, differentiation, and immunomodulation of MSCs decrease with aging and ex vivo expansion. The sirtuins have emerged as a class of protein deacylases involved in aging, oxidative stress, and metabolism...
2017: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/28715593/physical-exercise-improves-total-antioxidant-capacity-and-gene-expression-in-rat-hippocampal-tissue
#16
F Franzoni, G Federighi, J Fusi, E Cerri, R Banducci, A Petrocchi, A Innocenti, C Pruneti, S Daniele, S Pellegrini, C Martini, R Scuri, F Galetta
Exercise may exert beneficial effects on cognitive functions and play an important role in the prevention of neurodegenerative diseases. Such effects seem to be mediated by changes in anti-oxidative status, but limited information is available on the nature of molecular pathways supporting the antioxidant effects of exercise in the brain. In this study 3-5-month-old male Wistar albino rats were subjected to three times/week moderate intensity exercise on a rodent treadmill for a period of 6 weeks. The tissue antioxidant activity towards various reactive oxygen species (ROS) was determined in the hippocampus...
July 1, 2017: Archives Italiennes de Biologie
https://www.readbyqxmd.com/read/28711502/a-small-molecule-activator-of-sirt3-promotes-deacetylation-and-activation-of-manganese-superoxide-dismutase
#17
Jiaqi Lu, Hua Zhang, Xian Chen, Yong Zou, Jiasong Li, Li Wang, Minhao Wu, Jianye Zang, Yang Yu, Wei Zhuang, Qing Xia, Jiangyun Wang
The modulation of protein acetylation network is a promising strategy for life span extension and disease treatment (Sabari et al., 2016; Giblin et al., 2014) [1,2]. A variety of small molecules have been developed to target deacetylases, but extremely few of these molecules are capable of activating the mitochondrial NAD-dependent deacetylase sirtuin-3 (SIRT3) (Gertz and Steegborn, 2016; Scholz et al., 2015) [3,4]. Manganese superoxide dismutase (MnSOD) is the major superoxide scavenger in mitochondria, whose activity is regulated by SIRT3-mediated deacetylation, particularly at the Lys68 site (Chen et al...
July 12, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28707980/extranuclear-sirtuins-and-metabolic-stress
#18
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/28704962/sirt3-oncogene-and-tumor-suppressor-in-cancer
#19
REVIEW
Margalida Torrens-Mas, Jordi Oliver, Pilar Roca, Jorge Sastre-Serra
Sirtuin 3 (SIRT3), the major deacetylase in mitochondria, plays a crucial role in modulating oxygen reactive species (ROS) and limiting the oxidative damage in cellular components. SIRT3 targets different enzymes which regulate mitochondrial metabolism and participate in ROS detoxification, such as the complexes of the respiratory chain, the isocitrate dehydrogenase, or the manganese superoxide dismutase. Thus, SIRT3 activity is essential in maintaining mitochondria homeostasis and has recently received great attention, as it is considered a fidelity protein for mitochondrial function...
July 12, 2017: Cancers
https://www.readbyqxmd.com/read/28699360/mir-34a-and-mir-9-are-overexpressed-and-sirt-genes-are-downregulated-in-peripheral-blood-mononuclear-cells-of-aging-humans
#20
Magdalena Owczarz, Monika Budzinska, Anna Domaszewska-Szostek, Joanna Borkowska, Jacek Polosak, Magdalena Gewartowska, Przemyslaw Slusarczyk, Monika Puzianowska-Kuznicka
Increased expression of sirtuins lowers the risk of age-related diseases, while their role in the regulation of longevity is not firmly established. Since aging is associated with immunosenescence, we tested whether sirtuin expression was modified in peripheral blood mononuclear cells (PBMC) in an age-related manner and whether this might result from altered expression of the selected miRNAs. The expression of seven SIRT genes and of SIRT1 mRNA-interacting miR-9, miR-34a, miR-132, and miR-199a-5p was evaluated by real-time PCR in PBMC originating from young (Y, n = 57, mean age 27 ± 4...
August 2017: Experimental Biology and Medicine
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