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Tao Wang, Shao-Lei Geng, Yu-Min Guan, Wei-Hua Xu
Diapause in insects is akin to dauer in Caenorhabditis elegans and hibernation in vertebrates. Diapause causes a profound extension of lifespan by low metabolic activity. However, the detailed regulatory mechanisms for low metabolic activity remain unknown. Here, we showed that low pyruvate levels are present in the brains of diapause-destined pupae of the cotton bollworm Helicoverpa armigera , and three enzymes pyruvate kinase (PK), phosphoenolpyruvate carboxykinase (PEPCK), and phosphoglycerate mutase (PGAM) are closely correlated with pyruvate homeostasis...
May 16, 2018: Aging
Danhong Wu, Wenmei Lu, Zhenyu Wei, Ming Xu, Xueyuan Liu
No abstract text is available yet for this article.
May 9, 2018: Neuroscience
Qingling Yang, Shanjun Dai, Xiaoyan Luo, Jing Zhu, Fangyuan Li, Jinhao Liu, Guidong Yao, Yingpu Sun
The quality of postovulatory metaphase II oocytes undergoes a time-dependent deterioration as a result of the aging process. Melatonin is considered an anti-aging agent. However, the underlying mechanisms of how melatonin improves the quality of postovulatory aged oocytes remain largely unclear. In this study, by using mouse model, we found that there were elevated ROS levels and impaired mitochondrial function demonstrated by reduced mitochondrial membrane potential (ΔΨm) and increased mitochondrial aggregation in oocytes aged 24 h, accompanied by an increased number of meiotic errors, unregulated autophagy-related proteins and early apoptosis, which led to decreased oocyte quality and disrupted developmental competence...
May 11, 2018: Reproduction: the Official Journal of the Society for the Study of Fertility
David Romeo-Guitart, Tatiana Leiva-Rodríguez, María Espinosa-Alcantud, Núria Sima, Alejandro Vaquero, Helena Domínguez-Martín, Diego Ruano, Caty Casas
Sirtuin 1 (SIRT1) activity is neuroprotective, and we have recently demonstrated its role in the retrograde degenerative process in motoneurons (MNs) in the spinal cord of rats after peripheral nerve root avulsion (RA) injury. SIRT2 has been suggested to exert effects opposite those of SIRT1; however, its roles in neurodegeneration and neuron response after nerve injury remain unclear. Here we compared the neuroprotective potentials of SIRT1 activation and SIRT2 inhibition in a mouse model of hypoglossal nerve axotomy...
May 10, 2018: Cell Death & Disease
Li Yan, Xuemei Zhan, Zhongyao Jia, Lili Liu, Ning Jin
BACKGROUND: Altered expression of Sirtuin 2 (Sirt2) was associated with cancer development and progression. This study further assessed the association of Sirt2 expression with clinicopathological data and prognosis of patients with esophageal squamous cell carcinoma (ESCC) after postoperative concurrent chemoradiotherapy. METHODS: Tissue specimens from 95 ESCC patients were collected for immunohistochemical analysis of Sirt2 expression, which was used to determine association with patient clinicopathological and survival data...
May 1, 2018: Clinical Laboratory
Hui Wen, Nina Xue, Feng Wu, Yujun He, Gang Zhang, Zebin Hu, Huaqing Cui
Chromenone-derived natural products include chromones (flavone, isoflavone) and coumarins. Chromenone compounds not only exhibit impressive biological activities, but also are an important resource of experimentally used fluorophores, such as, 7-amino-4-methylcoumarin (AMC). Various chromenone compounds have reported to have weak fluorescence, and this has the potential to interfere with the measurements during AMC fluorogenic assays and result in non-robust assay readouts. Several flavones and isoflavones were found as SIRT1 activators, while fluorogenic sirtuin assays utilized AMC labelled peptides as the substrates...
May 2, 2018: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
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
Jorge M Pereira, Christine Chevalier, Thibault Chaze, Quentin Gianetto, Francis Impens, Mariette Matondo, Pascale Cossart, Mélanie A Hamon
Sirtuin 2 is a nicotinamide-adenine-dinucleotide-dependent deacetylase that regulates cell processes such as carcinogenesis, cell cycle, DNA damage, and infection. Subcellular localization of SIRT2 is crucial for its function but is poorly understood. Infection with the bacterial pathogen Listeria monocytogenes, which relocalizes SIRT2 from the cytoplasm to the chromatin, provides an ideal stimulus for the molecular study of this process. In this report, we provide a map of SIRT2 post-translational modification sites and focus on serine 25 phosphorylation...
April 24, 2018: Cell Reports
Saman Mohammadi Saravle, Manouchehr Ahmadi Hedayati, Ebrahim Mohammadi, Farshad Sheikhesmaeili, Bahram Nikkhou
Introduction: The World Health Organization has categorized Helicobacter pylori as a carcinogen for gastric cancer, which causes human mortality worldwide. A number of studies have shown that H. pylori affects cell signaling in gastric epithelial cells and changes the expression of some proteins such as proinflammatory cytokines. Bacterial infections may alter sirt1 and sirt2 genes expression in inflammatory tissues and cancer cells. In this study, sirt1 and sirt2 genes expression in gastric cancers was surveyed with reference to H...
April 25, 2018: Asian Pacific Journal of Cancer Prevention: APJCP
B Rocha, A R Rodrigues, I Tomada, M J Martins, J T Guimarães, A M Gouveia, H Almeida, D Neves
Background: Endothelial dysfunction underlies cardiovascular disease that frequently affects aged individuals. Characterized by local decrease in nitric oxide, it results from down-regulation of endothelial nitric oxide synthase (eNOS) expression/activity. Aiming to elucidate the molecular mechanisms involved in age-related endothelial dysfunction and to unveil potential therapeutic targets, we tested how diet pattern, exercise and atorvastatin modulate the expression of eNOS, inducible NOS (iNOS), endothelin-1, sirtuins (SIRT) and microRNA-155 in the erectile tissue of high-fat fed aged rats...
2018: Nutrition & Metabolism
Norio Kudo, Akihiro Ito, Mayumi Arata, Akiko Nakata, Minoru Yoshida
SIRT2 is a member of the human sirtuin family of proteins and possesses NAD+ -dependent lysine deacetylase/deacylase activity. SIRT2 has been implicated in carcinogenesis in various cancers including leukaemia and is considered an attractive target for cancer therapy. Here, we identified NPD11033, a selective small-molecule SIRT2 inhibitor, by a high-throughput screen using the RIKEN NPDepo chemical library. NPD11033 was largely inactive against other sirtuins and zinc-dependent deacetylases. Crystallographic analysis revealed a unique mode of action, in which NPD11033 creates a hydrophobic cavity behind the substrate-binding pocket after a conformational change of the Zn-binding small domain of SIRT2...
June 5, 2018: Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences
Sören Swyter, Matthias Schiedel, Daria Monaldi, Sándor Szunyogh, Attila Lehotzky, Tobias Rumpf, Judit Ovádi, Wolfgang Sippl, Manfred Jung
Sirtuins are NAD+ -dependent protein deacylases capable of cleaving off acetyl as well as other acyl groups from the ɛ-amino group of lysines in histones and other substrate proteins. They have been reported as promising drug targets, and thus modulators of their activity are needed as molecular tools to uncover their biological function and as potential therapeutics. Here, we present new assay formats that complement existing assays for sirtuin biochemistry and cellular target engagement. Firstly, we report the development of a homogeneous fluorescence-based activity assay using unlabelled acylated peptides...
June 5, 2018: Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences
Chin-Wei Liu, Ying-Chao Lin, Chao-Ming Hung, Bing-Lan Liu, Sheng-Chu Kuo, Chi-Tang Ho, Tzong-Der Way, Chih-Hsin Hung
Breast cancer is a major public health problem throughout the world. In this report, we investigated whether CHM-1, a novel synthetic antimitotic agent could be developed into a potent antitumor agent for treating human breast cancer. CHM-1 induced growth inhibition in MDA-MB-231, MDA-MB-453 and MCF-7 cells in a concentration-dependent manner. Importantly, CHM-1 is less toxic to normal breast (HBL-100) cells. CHM-1 interacted with tubulin, markedly inhibited tubulin polymerization, and disrupted microtubule organization...
April 18, 2018: Chemico-biological Interactions
Zahra Arab Sadeghabadi, Nasrin Ziamajidi, Roghayeh Abbasalipourkabir, Roohollah Mohseni
BACKGROUND: Diabetic nephropathy and liver damage are important complications of diabetes mellitus (DM). Various factors, such as sirtuins (silent information regulators or SIRTs) are associated with these complications. Sirtuins are a family of NAD+-dependent proteins, and seven types of these can be found in mammalians. In this study, we evaluated the effects of aqueous garlic extract (G) on the expressions of SIRT1 and SIRT2 genes in the kidney and liver tissues of rats with types 1 and 2 diabetes...
April 19, 2018: Journal of Basic and Clinical Physiology and Pharmacology
C Bétry, E Meugnier, M Pflieger, G Grenet, S Hercberg, P Galan, E Kesse-Guyot, H Vidal, M Laville
AIM: Ageing is often associated with metabolic abnormalities such as insulin resistance, although some people remain metabolically healthy throughout their lives. The aim of this study was to gain more insight into metabolic health with increasing age. METHODS: Two groups of robust and of frail subjects, respectively, were identified based on a composite ageing indicator and recruited from the French SU.VI.MAX 2 cohort of older disease-free subjects. In all, 14 men and 12 women, aged 67±4 years, with similar anthropometric and metabolic characteristics at baseline (BMI: 24...
February 12, 2018: Diabetes & Metabolism
Theresa Grohmann, Melanie Penke, Stefanie Petzold-Quinque, Susanne Schuster, Sandy Richter, Wieland Kiess, Antje Garten
NAMPT (Nicotinamide phosphoribosyltransferase) catalyses the rate-limiting step in the NAD biosynthesis from nicotinamide and thereby regulates the activity of NAD-dependent enzymes. Cancer cells are highly dependent on NAD for energy and DNA repair processes and are assumed to be more susceptible to an inhibition of NAD synthesis than non-transformed cells. We aimed to investigate whether or not inhibition of NAMPT with its specific inhibitor FK866 can sensitize leukemia cells for chemotherapeutic agents. NAMPT protein abundance, enzymatic activity and NAD concentrations were significantly higher in Jurkat and Molt-4 leukemia cell lines compared to normal peripheral blood mononuclear cells...
April 5, 2018: Leukemia Research
Fang-Fang He, Ren-Yu You, Chen Ye, Chun-Tao Lei, Hui Tang, Hua Su, Chun Zhang
BACKGROUND/AIMS: Renal tubular epithelial cells and fibroblasts are the main sources of myofibroblasts, and these cells produce the extracellular matrix during tubulointerstitial fibrosis (TIF). Histone deacetylases (HDAC) inhibitors exert an antifibrogenic effect in the skin, liver and lung. Sirtuin 2 (SIRT2), which is a class III HDAC, is an important member of NAD+-dependent protein deacetylases. The current study evaluated the role of SIRT2 in renal TIF. METHODS: Immunohistochemical staining and Western blot were performed to evaluate SIRT2 expression in TIF patients and unilateral urethral obstruction (UUO) mice...
March 26, 2018: Cellular Physiology and Biochemistry
Joel Isohookana, Kirsi-Maria Haapasaari, Ylermi Soini, Peeter Karihtala
BACKGROUND/AIM: The role of histone demethylators, such as Jumonji domain 2 (JMJD2/KDM4) proteins, and histone deacetylases, such as sirtuins (SIRT) is poorly characterized in pancreatic carcinomas while they have a major role in the carcinogenesis of several other tumours. MATERIALS AND METHODS: We assessed retrospectively with immunohistochemistry the expressions of KDM4A, KDM4B and KDM4D in 81 and SIRT1-4 in 102 pancreatic adenocarcinomas. Immunostaining was evaluated separately in benign pancreatic tissues and in malignant cells...
April 2018: Anticancer Research
Feng Zhang, Qing Zhou, Guiwen Yang, Liguo An, Fahui Li, Jiangyun Wang
Advances in acetylated protein-protein/DNA interactions depend on the development of a novel NMR (nuclear magnetic resonance) probe to study the conformational changes of acetylated proteins. However, the method for detecting the acetylated protein conformation is underdeveloped. Herein, an acetyllysine mimic has been exploited for detecting the conformational changes of acetylated p53-protein/DNA interactions by genetic code expansion and 19F NMR. This 19F NMR probe shows high structural similarity to acetyllysine and could not be deacetylated by sirtuin deacetylase in vitro/vivo...
March 29, 2018: Chemical Communications: Chem Comm
Takeshi Yasuda, Wataru Kagawa, Tomoo Ogi, Takamitsu A Kato, Takehiro Suzuki, Naoshi Dohmae, Kazuya Takizawa, Yuka Nakazawa, Matthew D Genet, Mika Saotome, Michio Hama, Teruaki Konishi, Nakako Izumi Nakajima, Masaharu Hazawa, Masanori Tomita, Manabu Koike, Katsuko Noshiro, Kenichi Tomiyama, Chizuka Obara, Takaya Gotoh, Ayako Ui, Akira Fujimori, Fumiaki Nakayama, Fumio Hanaoka, Kaoru Sugasawa, Ryuichi Okayasu, Penny A Jeggo, Katsushi Tajima
The p300 and CBP histone acetyltransferases are recruited to DNA double-strand break (DSB) sites where they induce histone acetylation, thereby influencing the chromatin structure and DNA repair process. Whether p300/CBP at DSB sites also acetylate non-histone proteins, and how their acetylation affects DSB repair, remain unknown. Here we show that p300/CBP acetylate RAD52, a human homologous recombination (HR) DNA repair protein, at DSB sites. Using in vitro acetylated RAD52, we identified 13 potential acetylation sites in RAD52 by a mass spectrometry analysis...
March 28, 2018: PLoS Genetics
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