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https://www.readbyqxmd.com/read/28726069/loss-of-sirtuin-4-leads-to-elevated-glucose-and-leucine-stimulated-insulin-levels-and-accelerated-age-induced-insulin-resistance-in-multiple-murine-genetic-backgrounds
#1
Frank K Huynh, Xiaoke Hu, Zhihong Lin, James D Johnson, Matthew D Hirschey
Several inherited metabolic disorders are associated with an accumulation of reactive acyl-CoA metabolites that can non-enzymatically react with lysine residues to modify proteins. While the role of acetylation is well-studied, the pathophysiological relevance of more recently discovered acyl modifications, including those found in inherited metabolic disorders, warrants further investigation. We recently showed that sirtuin 4 (SIRT4) removes glutaryl, 3-hydroxy-3-methylglutaryl, 3-methylglutaryl, and 3-methylglutaconyl modifications from lysine residues...
July 19, 2017: Journal of Inherited Metabolic Disease
https://www.readbyqxmd.com/read/28724806/nicotinamide-mononucleotide-requires-sirt3-to-improve-cardiac-function-and-bioenergetics-in-a-friedreich-s-ataxia-cardiomyopathy-model
#2
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/28720061/the-long-non-coding-rna-malat1-promotes-the-migration-and-invasion-of-hepatocellular-carcinoma-by-sponging-mir-204-and-releasing-sirt1
#3
Zhouhua Hou, Xuwen Xu, Ledu Zhou, Xiaoyu Fu, Shuhui Tao, Jiebin Zhou, Deming Tan, Shuiping Liu
Increasing evidence supports the significance of long non-coding RNA in cancer development. Several recent studies suggest the oncogenic activity of long non-coding RNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) in hepatocellular carcinoma. In this study, we explored the molecular mechanisms by which MALAT1 modulates hepatocellular carcinoma biological behaviors. We found that microRNA-204 was significantly downregulated in sh-MALAT1 HepG2 cell and 15 hepatocellular carcinoma tissues by quantitative real-time polymerase chain reaction analysis...
July 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28719070/sirtuin-1-attenuates-inflammation-and-hepatocellular-damage-in-liver-transplant-ischemia-reperfusion-from-mouse-to-human
#4
Kojiro Nakamura, Shoichi Kageyama, Bibo Ke, Takehiro Fujii, Rebecca A Sosa, Elaine F Reed, Nakul Datta, Ali Zarrinpar, Ronald W Busuttil, Jerzy W Kupiec-Weglinski
Hepatic ischemia-reperfusion injury (IRI), an inevitable antigen-independent inflammation response in cadaveric liver transplantation, correlates with poor early graft function, rejection episodes, and contributes to donor organ shortage. Sirtuin 1 (SIRT1) is a histone deacetylase which may regulate inflammatory cell activity and manage liver function in IRI, though its functional role and clinical relevance remains to be elucidated. We investigated the efficacy of SIRT1 activation in murine liver IRI model and verified the concept of putative SIRT1-mediated hepatoprotection in clinical liver transplantation...
July 18, 2017: Liver Transplantation
https://www.readbyqxmd.com/read/28719017/contrasting-sirtuin-and-parp-activity-of-selected-2-4-6-trisubstituted-benzimidazoles
#5
Keng Yoon Yeong, Soo Choon Tan, Chun-Wai Mai, Chee-Onn Leong, Felicia Fei-Lei Chung, Yean Kee Lee, Chin Fei Chee, Noorsaadah Abdul Rahman
Both sirtuin and poly(ADP-ribose)polymerase (PARP) family of enzymes utilize NAD+ as co-substrate. Inhibitors of sirtuins and PARPs are important tools in drug discovery as they are reported to be linked to multiple diseases such as cancer. New potent sirtuin inhibitors (2,4,6-trisubstituted benzimidazole) were discovered from reported PARP inhibitor scaffold. Interestingly, the synthesized compounds have contrasting sirtuin and PARP-1 inhibitory activity. We showed that modification on benzimidazoles may alter their selectivity towards sirtuin or PARP-1 enzymes...
July 18, 2017: Chemical Biology & Drug Design
https://www.readbyqxmd.com/read/28717923/mirna-200a-induce-cell-apoptosis-in-renal-cell-carcinoma-by-directly-targeting-sirt1
#6
Hao Fu, Wenke Song, Xuancai Chen, Tao Guo, Bin Duan, Xinxi Wang, Yachun Tang, Liang Huang, Chi Zhang
Accumulating evidence indicates that microRNAs are implicated in tumor initiation and progression through negatively regulating oncogenes or tumor suppressor genes. In the present study, we report that the expression of miR-200a was significantly lower in renal cell carcinoma (RCC) specimens and RCC cell lines. Restoration of miR-200a suppressed cell growth, arrested cell cycle progression, and promoted cell apoptosis in RCC cell lines. We next used qRT-PCR array technology to identify Sirtuin 1 (SIRT1) as one of the downregulated proteins during miR-200a overexpression in 786-O cells...
July 17, 2017: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/28717408/sirt3-enhances-mesenchymal-stem-cell-longevity-and-differentiation
#7
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
#8
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/28711923/acute-myeloid-leukemia-cells-require-6-phosphogluconate-dehydrogenase-for-cell-growth-and-nadph-dependent-metabolic-reprogramming
#9
Haymanti Bhanot, Ellen L Weisberg, Mamatha M Reddy, Atsushi Nonami, Donna Neuberg, Richard M Stone, Klaus Podar, Ravi Salgia, James D Griffin, Martin Sattler
Acute myeloid leukemia (AML) cells are highly dependent on glycolytic pathways to generate metabolic energy and support cell growth, hinting at specific, targetable vulnerabilities as potential novel targets for drug development. Elevated levels of NADPH, a central metabolic factor involved in redox reactions, are common in myeloid leukemia cells, but the significance or biochemical basis underlying this increase is unknown. Using a small molecule analog that efficiently inhibits NADPH-producing enzymes, we found that AML cells require NADPH homeostasis for cell growth...
June 28, 2017: Oncotarget
https://www.readbyqxmd.com/read/28711502/a-small-molecule-activator-of-sirt3-promotes-deacetylation-and-activation-of-manganese-superoxide-dismutase
#10
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.(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).(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.(5) To investigate the influence of Lys68 acetylation on MnSOD activity, we produced a mutant MnSOD protein-bearing N-acetyllysine (AcK) at its Lys68 position through the genetic code expansion approach...
July 12, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28708932/tandem-repeat-variation-near-the-hic1-hypermethylated-in-cancer-1-promoter-predicts-outcome-of-oxaliplatin-based-chemotherapy-in-patients-with-metastatic-colorectal-cancer
#11
Satoshi Okazaki, Marta Schirripa, Fotios Loupakis, Shu Cao, Wu Zhang, Dongyun Yang, Yan Ning, Martin D Berger, Yuji Miyamoto, Mitsukuni Suenaga, Syma Iqubal, Afsaneh Barzi, Chiara Cremolini, Alfredo Falcone, Francesca Battaglin, Lisa Salvatore, Beatrice Borelli, Timothy G Helentjaris, Heinz-Josef Lenz
BACKGROUND: The hypermethylated in cancer 1/sirtuin 1 (HIC1/SIRT1) axis plays an important role in regulating the nucleotide excision repair pathway, which is the main oxaliplatin-induced damage-repair system. On the basis of prior evidence that the variable number of tandem repeat (VNTR) sequence located near the promoter lesion of HIC1 is associated with HIC1 gene expression, the authors tested the hypothesis that this VNTR is associated with clinical outcome in patients with metastatic colorectal cancer who receive oxaliplatin-based chemotherapy...
July 14, 2017: Cancer
https://www.readbyqxmd.com/read/28708105/resveratrol-improves-glycemic-control-in-type-2-diabetic-obese-mice-by-regulating-glucose-transporter-expression-in-skeletal-muscle-and-liver
#12
Caio Y Yonamine, Erika Pinheiro-Machado, Maria L Michalani, Ana B Alves-Wagner, João V Esteves, Helayne S Freitas, Ubiratan F Machado
Insulin resistance participates in the glycaemic control disruption in type 2 diabetes mellitus (T2DM), by reducing muscle glucose influx and increasing liver glucose efflux. GLUT4 (Slc2a4 gene) and GLUT2 (Slc2a2 gene) proteins play a fundamental role in the muscle and liver glucose fluxes, respectively. Resveratrol is a polyphenol suggested to have an insulin sensitizer effect; however, this effect, and related mechanisms, have not been clearly demonstrated in T2DM. We hypothesized that resveratrol can improve glycaemic control by restoring GLUT4 and GLUT2 expression in muscle and liver...
July 14, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28708087/resveratrol-induced-amp-activated-protein-kinase-activation-is-cell-type-dependent-lessons-from-basic-research-for-clinical-application
#13
Fan Lan, Karen A Weikel, Jose M Cacicedo, Yasuo Ido
Despite the promising effects of resveratrol, its efficacy in the clinic remains controversial. We were the first group to report that the SIRT1 activator resveratrol activates AMP-activated protein kinase (AMPK) (Diabetes 2005; 54: A383), and we think that the variability of this cascade may be responsible for the inconsistency of resveratrol's effects. Our current studies suggest that the effect of SIRT1 activators such as resveratrol may not be solely through activation of SIRT1, but also through an integrated effect of SIRT1-liver kinase B1 (LKB1)-AMPK...
July 14, 2017: Nutrients
https://www.readbyqxmd.com/read/28707980/extranuclear-sirtuins-and-metabolic-stress
#14
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 ADP-ribosylation...
July 14, 2017: Antioxidants & Redox Signaling
https://www.readbyqxmd.com/read/28707979/emerging-roles-for-sirt5-in-metabolism-and-cancer
#15
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/28707004/host-sirtuin-1-regulates-mycobacterial-immunopathogenesis-and-represents-a-therapeutic-target-against-tuberculosis
#16
Catherine Y Cheng, Nuria M Gutierrez, Mardiana B Marzuki, Xiaohua Lu, Taylor W Foreman, Bhairav Paleja, Bernett Lee, Akhila Balachander, Jinmiao Chen, Liana Tsenova, Natalia Kurepina, Karen W W Teng, Kim West, Smriti Mehra, Francesca Zolezzi, Michael Poidinger, Barry Kreiswirth, Deepak Kaushal, Hardy Kornfeld, Evan W Newell, Amit Singhal
Mycobacterium tuberculosis (Mtb) executes a plethora of immune-evasive mechanisms, which contribute to its pathogenesis, limited efficacy of current therapy, and the emergence of drug-resistant strains. This has led to resurgence in attempts to develop new therapeutic strategies/targets against tuberculosis (TB). We show that Mtb down-regulates sirtuin 1 (SIRT1), a nicotinamide adenine dinucleotide (NAD(+))-dependent deacetylase, in monocytes/macrophages, TB animal models, and TB patients with active disease...
March 2017: Science Immunology
https://www.readbyqxmd.com/read/28706576/adherence-to-the-mediterranean-diet-and-circulating-levels-of-sirtuin-4-in-obese-patients-a-novel-association
#17
Luigi Barrea, Giovanni Tarantino, Carolina Di Somma, Giovanna Muscogiuri, Paolo Emidio Macchia, Andrea Falco, Annamaria Colao, Silvia Savastano
PURPOSE: This study was aimed at evaluating sirtuin 4 (Sirt4) levels in obese individuals, in relation to their adherence to the Mediterranean diet (MD), a healthy dietary pattern characterized by high antioxidant capacity, and markers of visceral fat storage. SUBJECTS/METHODS: Forty-three obese patients (44% males; BMI: 36.7-58.8 kg/m(2)) were consecutively included. PREvención con DIeta MEDiterránea (PREDIMED) and the 7-day food records were used to assess the adherence to MD and dietary pattern, respectively...
2017: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/28706491/early-life-exposure-to-lead-induces-cognitive-impairment-in-elder-mice-targeting-sirt1-phosphorylation-and-oxidative-alterations
#18
Lijie Zhang, Runqi Tu, Yawei Wang, Yazhen Hu, Xing Li, Xuemin Cheng, Yanyan Yin, Wenjie Li, Hui Huang
Pb is a potential risk factor for cognition, mainly mediated by enhanced oxidative stress. Resveratrol, a natural polyphenol with crucial anti-oxidative property, is recently implicated in preventing cognitive deficits in normal aging and neurodegenerative disorders. Its beneficial effects have been linked to sirtuin 1(SIRT1) activation. The aim of this work is to investigate the possible linkage between alterations in Pb-induced oxidative damage and cognitive impairment by prolonged treatment of resveratrol...
2017: Frontiers in Physiology
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/28704830/sirtuins-in-skin-and-skin-cancers
#20
Liz Mariely Garcia-Peterson, Melissa Jean Wilking-Busch, Mary Ann Ndiaye, Christine Gaby Azer Philippe, Vijayasaradhi Setaluri, Nihal Ahmad
The sirtuins are a family of proteins that comprise class III of the histone deacetylases. These NAD+-dependent proteins have been found to be intricately involved in a variety of important and skin-relevant cellular functions and processes, including aging, UV damage response, oxidative stress, and wound repair. In addition, recent research is unraveling the role of sirtuins in a variety of skin diseases, including melanoma and nonmelanoma skin cancers. In this review, we provide a discussion on the potential roles and implications of different sirtuins in skin-specific cellular processes, which may have relevance to skin health and skin diseases...
July 14, 2017: Skin Pharmacology and Physiology
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