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Sirtuins

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https://www.readbyqxmd.com/read/29150734/the-sirtuin-1-2-inhibitor-tenovin-1-induces-a-nonlinear-apoptosis-inducing-factor-dependent-cell-death-in-a-p53-null-ewing-s-sarcoma-cell-line
#1
Christian Marx, Lisa Marx-Blümel, Nora Lindig, René Thierbach, Doerte Hoelzer, Sabine Becker, Susan Wittig, Roland Lehmann, Hortense Slevogt, Thorsten Heinzel, Zhao-Qi Wang, James F Beck, Jürgen Sonnemann
The sirtuin 1/2 inhibitor tenovin-1 activates p53 and may have potential in the management of cancer. Here, we investigated the responsiveness of Ewing's sarcoma cells to tenovin-1. We examined its effects in two Ewing's sarcoma cell lines with different p53 status, i.e. in p53 wild-type and p53 null cells. Effects were assessed by flow cytometric analyses of cell death, mitochondrial membrane depolarization and reactive oxygen species (ROS) generation, by caspase 3/7 activity measurement, by mRNA expression profiling and by immunoblotting...
November 18, 2017: Investigational New Drugs
https://www.readbyqxmd.com/read/29150224/reduced-gene-expression-of-sirtuins-and-active-ampk-levels-in-children-and-adolescents-with-obesity-and-insulin-resistance
#2
Zahra Arab Sadeghabadi, Mitra Nourbakhsh, Parvin Pasalar, Solaleh Emamgholipour, Abolfazl Golestani, Bagher Larijani, Maryam Razzaghy-Azar
BACKGROUND: Sirtuins, including SIRT1 and SIRT2, are longevity-associated deacetylase enzymes that modulate metabolic homeostasis in response to the cellular energy state. Adenosine monophosphate activated protein kinase (AMPK) and SIRT1 are interrelated and share several common target pathways. This study aimed to evaluate the SIRT1 and SIRT2 gene expression in peripheral blood mononuclear cells (PBMCs) as well as plasma levels of AMPK, in obese children and adolescents. MATERIALS AND METHODS: Participants included 60 children and adolescents (30 obese and 30 age- and gender-matched control subjects)...
November 14, 2017: Obesity Research & Clinical Practice
https://www.readbyqxmd.com/read/29149454/melatonin-alleviates-adipose-inflammation-through-elevating-%C3%AE-ketoglutarate-and-diverting-adipose-derived-exosomes-to-macrophages-in-mice
#3
Zhenjiang Liu, Lu Gan, Tiantian Zhang, Qian Ren, Chao Sun
Obesity is associated with macrophage infiltration and metabolic inflammation, both of which promote metabolic disease progression. Melatonin is reported to possess anti-inflammatory properties by inhibiting inflammatory response of adipocytes and macrophages activation. However, the effects of melatonin on the communication between adipocytes and macrophages during adipose inflammation remain elusive. Here, we demonstrated melatonin alleviated inflammation and elevated α-ketoglutarate (αKG) level in adipose tissue of obese mice...
November 17, 2017: Journal of Pineal Research
https://www.readbyqxmd.com/read/29148265/resveratrol-ameliorates-the-severity-of-fibrogenesis-in-mice-with-experimental-chronic-pancreatitis
#4
Yixuan Xia, Hai-Tao Xiao, Kanglun Liu, Hong-Jie Zhang, Siu Wai Tsang
SCOPE: Resveratrol is generally considered beneficial to health-span and longevity since this dietary stilbenoid has been scrutinized for its activating property on the "rescue gene" sirtuin-1 that promotes cellular survival under stress. In addition to its antiaging property, our previous in vitro studies revealed that resveratrol notably inhibited the production of extracellular matrix (ECM) proteins in pancreatic stellate cells (PSCs), the classic effector cells against pancreatic injury...
November 16, 2017: Molecular Nutrition & Food Research
https://www.readbyqxmd.com/read/29147649/knockdown-of-sirt1-suppresses-bladder-cancer-cell-proliferation-and-migration-and-induces-cell-cycle-arrest-and-antioxidant-response-through-foxo3a-mediated-pathways
#5
Qingxuan Hu, Gang Wang, Jianping Peng, Guofeng Qian, Wei Jiang, Conghua Xie, Yu Xiao, Xinghuan Wang
Bladder cancer (BCa) is one of the most common tumors, but its underlying mechanism has not been fully clarified. Our transcriptome analysis suggested a close link of Sirtuins, Peroxisome Proliferator-Activated Receptor (PPAR), cell cycle regulation, reactive oxygen species (ROS) metabolism, and Forkhead Box Class O (FOXO) signaling pathway in BCa. SIRT1 is a key member of Sirtuins, playing important roles in aging and energy metabolism, which has been reported to be involved in various metabolic diseases and tumors...
2017: BioMed Research International
https://www.readbyqxmd.com/read/29145149/sirt2-decreases-atherosclerotic-plaque-formation-in-low-density-lipoprotein-receptor-deficient-mice-by-modulating-macrophage-polarization
#6
BuChun Zhang, YanFeng Ma, ChuHan Xiang
Compelling evidence has demonstrated that the M1 macrophage phenotype is central to atherosclerotic lesion development. SIRT2, an NAD(+)-dependent sirtuin deacetylase, is involved in modulating macrophage polarization. However, the role of SIRT2 in atherosclerotic progression remains unknown. Female LDL receptor knockout (LDLr(-/-)) mice were randomly divided into four groups for treatment with saline, empty lentivirus, lentivirus-SIRT2, or shRNA-SIRT2 for 4 weeks. Thereafter, the mice were fed an atherogenic high-fat diet (HFD) for another 8 weeks...
November 13, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29138829/resveratrol-ameliorates-inflammatory-damage-and-protects-against-osteoarthritis-in-a-rat-model-of-osteoarthritis
#7
Yulong Wei, Jie Jia, Xin Jin, Wei Tong, Hongtao Tian
Resveratrol is a non‑flavonoid polyphenol compound with a stilbene structure. As a type of phytoalexin produced under stress in plants, it improves the plant's resistance against pathogens and environment deterioration, and performs important functions beneficial to human health, such as anti‑cancer, anti‑oxidation, regulating blood lipid levels and prolonging life span. The effects of resveratrol were examined in a rat model of osteoarthritis (OA) and observed to ameliorate inflammatory damage and protect against OA...
November 13, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29138805/extracellular-polysaccharides-purified-from-aureobasidium-pullulans-sm%C3%A2-2001-polycan-inhibit-dexamethasone%C3%A2-induced-muscle-atrophy-in-mice
#8
Jong-Min Lim, Young Joon Lee, Hyung-Rae Cho, Dong-Chan Park, Go-Woon Jung, Sae Kwang Ku, Jae-Suk Choi
The present study assessed the beneficial skeletal muscle‑preserving effects of extracellular polysaccharides from Aureobasidium pullulans SM‑2001 (Polycan) (EAP) on dexamethasone (DEXA)‑induced catabolic muscle atrophy in mice. To investigate whether EAP prevented catabolic DEXA‑induced muscle atrophy, and to examine its mechanisms of action, EAP (100, 200 and 400 mg/kg) was administered orally, once a day for 24 days. EAP treatment was initiated 2 weeks prior to DEXA treatment (1 mg/kg, once a day for 10 days) in mice...
November 10, 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/29138502/crystal-structures-of-the-mitochondrial-deacylase-sirtuin-4-reveal-isoform-specific-acyl-recognition-and-regulation-features
#9
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/29136592/human-sirtuin-3-sirt3-deacetylates-histone-h3-lysine-56-to-promote-nonhomologous-end-joining-repair
#10
Amrita Sengupta, Devyani Haldar
Human sirtuin 3 (SIRT3) is a conserved NAD(+) dependent deacetylase, which functions in important cellular processes including transcription, metabolism, oxidative stress response. It is a robust mitochondrial deacetylase; however, few studies have indicated its nuclear functions. Here we report interaction of SIRT3 with core histones and identified acetylated histone H3 lysine 56 (H3K56ac) as its novel substrate, in addition to known substrates acetylated H4K16 and H3K9. Further, we showed in response to DNA damage SIRT3 localizes to the repair foci colocalizing with γH2AX and nonhomologous end joining (NHEJ) marker p53-binding protein 1 (53BP1)...
November 8, 2017: DNA Repair
https://www.readbyqxmd.com/read/29136322/heme-oxygenase-1-regulates-sirtuin-1-autophagy-pathway-in-liver-transplantation-from-mouse-to-human
#11
Kojiro Nakamura, Shoichi Kageyama, Shi Yue, Jing Huang, Takehiro Fujii, Bibo Ke, Rebecca A Sosa, Elaine F Reed, Nakul Datta, Ali Zarrinpar, Ronald W Busuttil, Jerzy W Kupiec-Weglinski
Liver ischemia-reperfusion injury (IRI) represents a major risk factor of early graft dysfunction and a key obstacle to expanding the donor pool in orthotopic liver transplantation (OLT). Although graft autophagy is essential for resistance against hepatic IRI, its significance in clinical OLT remains unknown. Despite recent data identifying heme oxygenase-1 (HO-1) as a putative autophagy inducer, its role in OLT and interactions with Sirtuin-1 (SIRT1), a key autophagy regulator, have not been studied. We aimed to examine HO-1 mediated autophagy induction in human OLT and in a murine OLT model with extended (20h) cold storage, as well as to analyze the requirement for SIRT1 in autophagy regulation by HO-1...
November 14, 2017: American Journal of Transplantation
https://www.readbyqxmd.com/read/29135935/tucum-do-cerrado-bactris-setosa-mart-may-promote-anti-aging-effect-by-upregulating-sirt1-nrf2-pathway-and-attenuating-oxidative-stress-and-inflammation
#12
Marcela de Sá Barreto da Cunha, Sandra Fernandes Arruda
Aging may be related to oxidative damage accumulation and a low-grade inflammation, both responses are modulated by iron and phytochemicals. This study investigated the effect of tucum-do-cerrado (Bactris setosa Mart.) consumption on the expression of sirtuins (SIRT 1 and 3) and senescence marker protein-30 (SMP30), and on the redox and inflammatory responses, in adult rats supplemented or not with dietary iron. Male Wistar rats were treated for 12 weeks with: control diet (CT); iron enriched-diet (+Fe); control diet + 15% tucum-do-cerrado (Tuc); or iron enriched-diet + 15% tucum-do-cerrado (Tuc + Fe)...
November 14, 2017: Nutrients
https://www.readbyqxmd.com/read/29134718/sirt1-exhibits-antioxidative-effects-in-ht22-cells-induced-by-tert-butyl-alcohol
#13
Junxiang Ma, Dongmei Song, Yuanyuan Zhang, Li Chen, Shixuan Zhang, Jiaxin Jia, Tian Chen, Caixia Guo, Lin Tian, Ai Gao, Piye Niu
Tertiary butyl alcohol (TBA) is a principal metabolite of methyl tertiary-butyl ether (MTBE), a common pollutant worldwide in the ground or underground water, which is found to produce nervous system damage. Nevertheless, few data regarding the effects of TBA has been reported. Studies indicated that oxidative stress plays a pivotal role in MTBE neurotoxic mechanism. Sirtuin 1 (SIRT1) has been reported to exert a neuroprotective effect on various neurologic diseases via resistance to oxidative stress by deacetylating its substrates...
November 14, 2017: Environmental Toxicology
https://www.readbyqxmd.com/read/29133780/o-glcnacylation-of-sirt1-enhances-its-deacetylase-activity-and-promotes-cytoprotection-under-stress
#14
Cuifang Han, Yuchao Gu, Hui Shan, Wenyi Mi, Jiahui Sun, Minghui Shi, Xinling Zhang, Xinzhi Lu, Feng Han, Qianhong Gong, Wengong Yu
SIRT1 is the most evolutionarily conserved mammalian sirtuin, and it plays a vital role in the regulation of metabolism, stress responses, genome stability, and ageing. As a stress sensor, SIRT1 deacetylase activity is significantly increased during stresses, but the molecular mechanisms are not yet fully clear. Here, we show that SIRT1 is dynamically modified with O-GlcNAc at Ser 549 in its carboxy-terminal region, which directly increases its deacetylase activity both in vitro and in vivo. The O-GlcNAcylation of SIRT1 is elevated during genotoxic, oxidative, and metabolic stress stimuli in cellular and mouse models, thereby increasing SIRT1 deacetylase activity and protecting cells from stress-induced apoptosis...
November 14, 2017: Nature Communications
https://www.readbyqxmd.com/read/29132743/nuclear-sirtuins-and-inflammatory-signaling-pathways
#15
REVIEW
Keila Lopes Mendes, Deborah de Farias Lelis, Sérgio Henrique Sousa Santos
The regulation of chronic inflammation has received considerable research attention in recent years because of its contribution to the pathogenesis of chronic diseases such as arthritis, diabetes, metabolic syndrome and obesity. Thus, strategies that inhibit the inflammatory state may be beneficial in improving the pathophysiology of several inflammation-related disorders. Sirtuins are a family of histone deacetylases that contain seven enzymatic activities in mammals (SIRT1-SIRT7) and function to suppress gene transcription by epigenetic mechanisms...
November 7, 2017: Cytokine & Growth Factor Reviews
https://www.readbyqxmd.com/read/29130578/sirt3-deregulation-is-linked-to-mitochondrial-dysfunction-in-alzheimer-s-disease
#16
Junghee Lee, Yunha Kim, Tian Liu, Yu Jin Hwang, Seung Jae Hyeon, Hyeonjoo Im, Kyungeun Lee, Victor E Alvarez, Ann C McKee, Soo-Jong Um, Manwook Hur, Inhee Mook-Jung, Neil W Kowall, Hoon Ryu
Alzheimer's disease (AD) is the leading cause of dementia in the elderly. Despite decades of study, effective treatments for AD are lacking. Mitochondrial dysfunction has been closely linked to the pathogenesis of AD, but the relationship between mitochondrial pathology and neuronal damage is poorly understood. Sirtuins (SIRT, silent mating type information regulation 2 homolog in yeast) are NAD-dependent histone deacetylases involved in aging and longevity. The objective of this study was to investigate the relationship between SIRT3 and mitochondrial function and neuronal activity in AD...
November 11, 2017: Aging Cell
https://www.readbyqxmd.com/read/29129747/mitochondrial-sirt3-and-neurodegenerative-brain-disorders
#17
REVIEW
Anamika, Archita Khanna, Papia Acharjee, Arup Acharjee, Surendra Kumar Trigun
Sirtuins are highly conserved NAD(+) dependent class III histone deacetylases and catalyze deacetylation and ADP ribosylation of a number of non-histone proteins. Since, they require NAD(+) for their activity, the cellular level of Sirtuins represents redox status of the cells and thereby serves as bona fide metabolic stress sensors. Out of seven homologues of Sirtuins identified in mammals, SIRT3, 4 & 5 have been found to be localized and active in mitochondria. During recent past, clusters of protein substrates for SIRT3 have been identified in mitochondria and thereby advocating SIRT3 as the main mitochondrial Sirtuin which could be involved in protecting stress induced mitochondrial integrity and energy metabolism...
November 9, 2017: Journal of Chemical Neuroanatomy
https://www.readbyqxmd.com/read/29129681/decreased-sirtuin-deacetylase-activity-in-lrrk2-g2019s-ipsc-derived-dopaminergic-neurons
#18
Andrew J Schwab, Samantha L Sison, Michael R Meade, Katarzyna A Broniowska, John A Corbett, Allison D Ebert
Mitochondrial changes have long been implicated in the pathogenesis of Parkinson's disease (PD). The glycine to serine mutation (G2019S) in leucine-rich repeat kinase 2 (LRRK2) is the most common genetic cause for PD and has been shown to impair mitochondrial function and morphology in multiple model systems. We analyzed mitochondrial function in LRRK2 G2019S induced pluripotent stem cell (iPSC)-derived neurons to determine whether the G2019S mutation elicits similar mitochondrial deficits among central and peripheral nervous system neuron subtypes...
October 31, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/29125913/standardized-kaempferia-parviflora-extract-enhances-exercise-performance-through-activation-of-mitochondrial-biogenesis
#19
Mi-Bo Kim, Taeyoon Kim, Changhee Kim, Jae-Kwan Hwang
Exercise enhances mitochondrial biogenesis in skeletal muscle. Increased mitochondrial function and content can contribute to the improvement in skeletal muscle function and the benefits of exercise by increasing the response to energy demands. The effect of standardized Kaempferia parviflora extract (KPE) on exercise performance was accessed in L6 myotubes and C57BL/6J mice. KPE significantly activated peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α) and increased mitochondrial density in L6 myotubes...
November 10, 2017: Journal of Medicinal Food
https://www.readbyqxmd.com/read/29123988/genetically-encoding-thioacetyl-lysine-as-a-non-deacetylatable-analog-of-lysine-acetylation-in-escherichia-coli
#20
Sumana Venkat, Dharma Theja Nannapaneni, Caroline Gregory, Qinglei Gan, Matt McIntosh, Chenguang Fan
Reversible lysine acetylation is one of the most widely distributed post-translational modifications; it is involved in a variety of biological processes and can be found in all three domains of life. Acetyltransferases and deacetylases work coordinately to control levels of protein acetylation. In this work, we applied the genetic code expansion strategy to site-specifically incorporate N(ε)-thioacetyl-l-lysine (TAcK) as an analog of N(ε)-acetyl-l-lysine (AcK) into green fluorescent protein and malate dehydrogenase in Escherichia coli...
November 2017: FEBS Open Bio
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