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Sirtuin

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https://www.readbyqxmd.com/read/28634568/sirtuin-2-protects-neural-cells-from-oxidative-stress-and-is-elevated-in-neurodegeneration
#1
Preeti Singh, Peter S Hanson, Christopher M Morris
Sirtuins are highly conserved lysine deacetylases involved in ageing, energy production, and lifespan extension. The mammalian SIRT2 has been implicated in Parkinson's disease (PD) where studies suggest SIRT2 promotes neurodegeneration. We therefore evaluated the effects of SIRT2 manipulation in toxin treated SH-SY5Y cells and determined the expression and activity of SIRT2 in postmortem brain tissue from patients with PD. SH-SY5Y viability in response to oxidative stress induced by diquat or rotenone was measured following SIRT2 overexpression or inhibition of deacetylase activity, along with α-synuclein aggregation...
2017: Parkinson's Disease
https://www.readbyqxmd.com/read/28634345/sirtuin-3-deficiency-does-not-alter-host-defenses-against-bacterial-and-fungal-infections
#2
Eleonora Ciarlo, Tytti Heinonen, Jérôme Lugrin, Hans Acha-Orbea, Didier Le Roy, Johan Auwerx, Thierry Roger
Sirtuin 3 (SIRT3) is the main mitochondrial deacetylase. SIRT3 regulates cell metabolism and redox homeostasis, and protects from aging and age-associated pathologies. SIRT3 may drive both oncogenic and tumor-suppressive effects. SIRT3 deficiency has been reported to promote chronic inflammation-related disorders, but whether SIRT3 impacts on innate immune responses and host defenses against infections remains essentially unknown. This aspect is of primary importance considering the great interest in developing SIRT3-targeted therapies...
June 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28632727/post-translational-regulation-contributes-to-the-loss-of-lkb1-expression-through-sirt1-deacetylase-in-osteosarcomas
#3
Nadège Presneau, Laure Alice Duhamel, Hongtao Ye, Roberto Tirabosco, Adrienne M Flanagan, Malihe Eskandarpour
BACKGROUND: The most prevalent form of bone cancer is osteosarcoma (OS), which is associated with poor prognosis in case of metastases formation. Mice harbouring liver kinase B1 (LKB1(+/-)) develop osteoblastoma-like tumours. Therefore, we asked whether loss of LKB1 gene has a role in the pathogenesis of human OS. METHODS: Osteosarcomas (n=259) were screened for LKB1 and sirtuin 1 (SIRT1) protein expression using immunohistochemistry and western blot. Those cases were also screened for LKB1 genetic alterations by next-generation sequencing, Sanger sequencing, restriction fragment length polymorphism and fluorescence in situ hybridisation approaches...
June 20, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28628306/lysine-deacetylation-by-hdac6-regulates-the-kinase-activity-of-akt-in-human-neural-progenitor-cells
#4
Jonathan Iaconelli, Jasmin Lalonde, Bradley Watmuff, Bangyan Liu, Ralph Mazitschek, Stephen J Haggarty, Rakesh Karmacharya
AKT family of serine-threonine kinases functions downstream of phosphatidylinositol 3-kinase (PI3K) to transmit signals by direct phosphorylation of a number of targets, including the mammalian target of rapamycin (mTOR), glycogen synthase kinase 3β (GSK3β) and β-catenin. AKT binds to phosphatidylinositol (3,4,5)-triphosphate (PIP3) generated by PI3K activation, which results in its membrane localization and subsequent activation through phosphorylation by phosphoinositide-dependent protein kinase 1 (PDK1)...
June 19, 2017: ACS Chemical Biology
https://www.readbyqxmd.com/read/28627583/deoxyactein-protects-pancreatic-%C3%AE-cells-against-methylglyoxal-induced-oxidative-cell-damage-by-the-upregulation-of-mitochondrial-biogenesis
#5
Kwang Sik Suh, Eun Mi Choi, Woon-Won Jung, Yu Jin Kim, Soo Min Hong, So Yong Park, Sang Youl Rhee, Suk Chon
Methylglyoxal (MG) is one of the major precursors of advanced glycation end products (AGEs), which are considered to be one of the causes of diabetes and its complications. The root and rhizomes of black cohosh (Cimicifuga racemosa) have long been used medicinally, and deoxyactein is one of its major constituents. In the present study, the protective effects of deoxyactein against MG-induced oxidative cell damage were investigated in insulin-producing pancreatic β-cells. We found that deoxyactein protected the pancreatic β-cells against MG-induced cell death...
June 12, 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/28627522/dot1l-safeguards-cartilage-homeostasis-and-protects-against-osteoarthritis
#6
Silvia Monteagudo, Frederique M F Cornelis, Carolina Aznar-Lopez, Ploi Yibmantasiri, Laura-An Guns, Peter Carmeliet, Frédéric Cailotto, Rik J Lories
Osteoarthritis is the most prevalent and crippling joint disease, and lacks curative treatment, as the underlying molecular basis is unclear. Here, we show that DOT1L, an enzyme involved in histone methylation, is a master protector of cartilage health. Loss of DOT1L disrupts the molecular signature of healthy chondrocytes in vitro and causes osteoarthritis in mice. Mechanistically, the protective function of DOT1L is attributable to inhibition of Wnt signalling, a pathway that when hyper-activated can lead to joint disease...
June 19, 2017: Nature Communications
https://www.readbyqxmd.com/read/28626222/the-role-of-epigenetics-in-renal-ageing
#7
REVIEW
Paul G Shiels, Dagmara McGuinness, Maria Eriksson, Jeroen P Kooman, Peter Stenvinkel
An ability to separate natural ageing processes from processes specific to morbidities is required to understand the heterogeneity of age-related organ dysfunction. Mechanistic insight into how epigenetic factors regulate ageing throughout the life course, linked to a decline in renal function with ageing, is already proving to be of value in the analyses of clinical and epidemiological cohorts. Noncoding RNAs provide epigenetic regulatory circuits within the kidney, which reciprocally interact with DNA methylation processes, histone modification and chromatin...
June 19, 2017: Nature Reviews. Nephrology
https://www.readbyqxmd.com/read/28624356/vascular-ageing-underlying-mechanisms-and-clinical-implications
#8
REVIEW
Ageliki Laina, Konstantinos Stellos, Kimon Stamatelopoulos
Epidemiological studies have shown that ageing is a major non-reversible risk factor for cardiovascular disease. Vascular ageing starts early in life and is characterized by a gradual change of vascular structure and function resulting in increased arterial stiffening. At the present review we discuss the role of the most important molecular pathways involved in vascular ageing, their association with arterial stiffening and possible novel therapeutic targets that may delay this otherwise irreversible degenerating process...
June 14, 2017: Experimental Gerontology
https://www.readbyqxmd.com/read/28623141/sirtuin-7-dependent-deacetylation-of-ddb1-regulates-the-expression-of-nuclear-receptor-tr4
#9
Md Fazlul Karim, Tatsuya Yoshizawa, Shihab U Sobuz, Yoshifumi Sato, Kazuya Yamagata
Sirtuin 7 (SIRT7) is an NAD(+)-dependent deacetylase/deacylase, but only a limited number of SIRT7 substrates have been identified. Recently, we found that Sirt7 knockout mice are resistant to high-fat diet-induced fatty liver, and that SIRT7 positively regulates the protein level of TR4, a nuclear receptor involved in lipid metabolism, by inhibiting the CUL4B/DDB1/DCAF1 E3 ubiquitin ligase complex. However, the mechanism by which SIRT7 inhibits the E3 ubiquitin ligase complex was not identified. Here, we demonstrate that SIRT7 binds directly to DDB1 and deacetylates DDB1 at Lys1121...
June 13, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28621732/lipid-accumulation-in-hepg2-cells-is-attenuated-by-strawberry-extract-through-ampk-activation
#10
Tamara Y Forbes-Hernández, Francesca Giampieri, Massimiliano Gasparrini, Sadia Afrin, Luca Mazzoni, Mario D Cordero, Bruno Mezzetti, José L Quiles, Maurizio Battino
Regulation of lipid metabolism is essential for treatment and prevention of several chronic diseases such as obesity, diabetes, and cardiovascular diseases, which are responsible for most deaths worldwide. It has been demonstrated that the AMP-activated protein kinase (AMPK) has a direct impact on lipid metabolism by modulating several downstream-signaling components. The main objective of the present work was to evaluate the in vitro effect of a methanolic strawberry extract on AMPK and its possible repercussion on lipid metabolism in human hepatocellular carcinoma cells (HepG2)...
June 16, 2017: Nutrients
https://www.readbyqxmd.com/read/28621682/melatonin-inhibits-sirt1-dependent-nampt-and-nfat5-signaling-in-chondrocytes-to-attenuate-osteoarthritis
#11
Jia Yi Guo, Feng Li, Yong Bing Wen, Hong Xun Cui, Ma Long Guo, Lin Zhang, Yun Fei Zhang, Yan Jin Guo, Yan Xing Guo
Osteoarthritis (OA) is a degenerative joint disease mainly characterized by cartilage degradation. Interleukin-1β (IL-1β) contributes to OA pathogenesis by enhancing oxidative stress and inflammation. Melatonin reportedly elicits potent protection against OA. However, the role of melatonin and underlying mechanism in IL-1β-stimulated chondrocytes remain largely unclear. In this study, we found that melatonin inhibited IL-1β-induced toxicity and sirtuin 1 (Sirt1) enhancement in human chondrocytes. Melatonin reduced the IL-1β-increased nicotinamide phosphoribosyltransferase (NAMPT) expression and the NAD+ level in chondrocytes in a Sirt1-dependent manner...
June 3, 2017: Oncotarget
https://www.readbyqxmd.com/read/28616572/reversible-lysine-acetylation-regulates-nuclear-translocation-of-tyrrs-to-counteract-genotoxic-oxidative-stress
#12
Chaoqun Li, Wei Yu
Aminoacyl-tRNA synthetases, catalyzing the first step of protein synthesis, have been shown to involve with multiple additional physiologic responses. Here, we summarize our findings that p300/CBP-Associated Factor and Sirtuin 1 play the reversible acetylation role in regulating the nuclear translocation of Tyrosyl-tRNA synthetase and activating transcription factor E2F1, thus facilitating the repair of damaged DNA.
2017: Molecular & Cellular Oncology
https://www.readbyqxmd.com/read/28615249/reduction-in-podocyte-sirt1-accelerates-kidney-injury-in-aging-mice
#13
Peter Y Chuang, Weijing Cai, Xuezhu Li, Lu Fang, Jin Xu, Rabi Yacoub, John Cijiang He, Kyung Lee
Both the incidence and prevalence of chronic kidney disease are increasing in the elderly population. Although aging is known to induce kidney injury, the underlying molecular mechanisms remain unclear. Sirtuin 1 (Sirt1), a longevity gene, is known to protect kidney cell injury from various cellular stresses. In previous studies, we showed that the podocyte-specific loss of Sirt1 aggravates diabetic kidney injury. However, the role of Sirt1 in aging-induced podocyte injury is not known. Therefore, in this study we sought to determine the effects of podocyte-specific reduction of Sirt1 in age-induced kidney injury...
June 14, 2017: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/28614912/peroxisome-proliferator-activated-receptor-alpha-facilitates-osteogenic-differentiation-in-mc3t3-e1-cells-via-the-sirtuin-1-dependent-signaling-pathway
#14
Kai Gong, Bo Qu, Cairu Wang, Jingsong Zhou, Dongfa Liao, Wei Zheng, Xianming Pan
Type 2 diabetes mellitus (T2DM) is a chronic, metabolic disease characterized by a lack of insulin and high glucose levels. T2DM can cause bone loss and fracture, thus leading to diabetic osteoporosis. Promoting osteogenic differentiation of osteoblasts may effectively treat diabetic osteoporosis. We previously reported that Sirtuin 1 (Sirt1), a NAD+-dependent deacetylase, promotes osteogenic differentiation through downregulation of peroxisome proliferator-activated receptor (PPAR) gamma. We also found that miR-132 regulates osteogenic differentiation by downregulating Sirt1 in a PPARbeta/δ- dependent manner...
June 14, 2017: Molecules and Cells
https://www.readbyqxmd.com/read/28613014/raising-the-list-of-sirt7-targets-to-a-new-level
#15
Nicolas G Simonet, Alejandro Vaquero
Sirtuins are crucial proteins involved in sensing and coordinating the response to different forms of stress, mainly through NAD(+) -dependent deacetylation of proteins. For that reason, sirtuins are directly involved in many human pathologies including cancer, diabetes, cardiovascular and neurodegenerative diseases. SirT7, one of the less well-understood sirtuins, has been associated with ribosome biogenesis, gene expression, metabolism and cancer. Despite the wide range of these functions, only a handful of targets for SirT7 have so far been described...
June 14, 2017: Proteomics
https://www.readbyqxmd.com/read/28611683/pathways-that-regulate-ros-scavenging-enzymes-and-their-role-in-defense-against-tissue-destruction-in-periodontitis
#16
REVIEW
Hiroyuki Kanzaki, Satoshi Wada, Tsuyoshi Narimiya, Yuuki Yamaguchi, Yuta Katsumata, Kanako Itohiya, Sari Fukaya, Yutaka Miyamoto, Yoshiki Nakamura
Periodontitis, an inflammatory disease that affects the tissues surrounding the teeth, is a common disease worldwide. It is caused by a dysregulation of the host inflammatory response to bacterial infection, which leads to soft and hard tissue destruction. In particular, it is the excessive inflammation in response to bacterial plaque that leads to the release of reactive oxygen species (ROS) from neutrophils, which, then play a critical role in the destruction of periodontal tissue. Generally, ROS produced from immune cells exhibit an anti-bacterial effect and play a role in host defense and immune regulation...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/28611316/effects-of-resveratrol-curcumin-berberine-and-other-nutraceuticals-on-aging-cancer-development-cancer-stem-cells-and-micrornas
#17
James A McCubrey, Kvin Lertpiriyapong, Linda S Steelman, Steve L Abrams, Li V Yang, Ramiro M Murata, Pedro L Rosalen, Aurora Scalisi, Luca M Neri, Lucio Cocco, Stefano Ratti, Alberto M Martelli, Piotr Laidler, Joanna Dulińska-Litewka, Dariusz Rakus, Agnieszka Gizak, Paolo Lombardi, Ferdinando Nicoletti, Saverio Candido, Massimo Libra, Giuseppe Montalto, Melchiorre Cervello
Natural products or nutraceuticals have been shown to elicit anti-aging, anti-cancer and other health-enhancing effects. A key target of the effects of natural products may be the regulation of microRNA (miR) expression which results in cell death or prevents aging, diabetes, cardiovascular and other diseases. This review will focus on a few natural products, especially on resveratrol (RES), curcumin (CUR) and berberine (BBR). RES is obtained from the skins of grapes and other fruits and berries. RES may extend human lifespan by activating the sirtuins and SIRT1 molecules...
June 12, 2017: Aging
https://www.readbyqxmd.com/read/28608449/resveratrol-suppresses-lipoprotein-associated-phospholipase-a2-expression-by-reducing-oxidative-stress-in-macrophages-and-animal-models
#18
Shengnan Sun, Mingjun Zhang, Qiangbing Yang, Ziying Shen, Jiahuan Chen, Biao Yu, He Wang, Jiali Qu, Daxin Pang, Wenzhi Ren, Hongsheng Ouyang, Xiaochun Tang
SCOPE: Resveratrol is a naturally occurring polyphenolic compound with known cardioprotective, anti-inflammatory and antioxidant properties. Lipoprotein-associated phospholipase A2 (Lp-PLA2 ) is associated with the risk of cardiovascular disease. Here, we investigated the effects of resveratrol on Lp-PLA2 expression in vitro and in vivo and explored the underlying mechanisms. METHODS AND RESULTS: Human monocytic cells (THP-1) were induced to differentiate into macrophages for an in vitro experimental model...
June 13, 2017: Molecular Nutrition & Food Research
https://www.readbyqxmd.com/read/28607107/myeloid-sirtuin-6-deficiency-causes-insulin-resistance-in-high-fat-diet-fed-mice-by-eliciting-macrophage-polarization-toward-an-m1-phenotype
#19
Youngyi Lee, Sun-O Ka, Hye-Na Cha, Yu-Na Chae, Mi-Kyung Kim, So-Young Park, Eun Ju Bae, Byung-Hyun Park
Obesity-related insulin resistance is closely associated with macrophage accumulation and subsequent cytokine release in local tissues. Sirtuin (Sirt) 6 is known to exert an anti-inflammatory function but its role in macrophages in the context of obesity has not been investigated. Here, we generated myeloid-specific Sirt6 knockout mice (mS6KO) and investigated the metabolic characteristics after high-fat diet (HFD) feeding for 16 weeks. Compared with their wild type littermates, HFD-fed mS6KO mice exhibited greater increases in body weight, fasting blood glucose- and insulin-levels, hepatic steatosis, glucose intolerance, and insulin resistance...
June 12, 2017: Diabetes
https://www.readbyqxmd.com/read/28603486/comparison-of-sirtuin-3-levels-in-als-and-huntington-s-disease-differential-effects-in-human-tissue-samples-vs-transgenic-mouse-models
#20
Eva Buck, Hanna Bayer, Katrin S Lindenberg, Johannes Hanselmann, Noemi Pasquarelli, Albert C Ludolph, Patrick Weydt, Anke Witting
Neurodegenerative diseases are characterized by distinct patterns of neuronal loss. In amyotrophic lateral sclerosis (ALS) upper and lower motoneurons degenerate whereas in Huntington's disease (HD) medium spiny neurons in the striatum are preferentially affected. Despite these differences the pathophysiological mechanisms and risk factors are remarkably similar. In addition, non-neuronal features, such as weight loss implicate a dysregulation in energy metabolism. Mammalian sirtuins, especially the mitochondrial NAD+ dependent sirtuin 3 (SIRT3), regulate mitochondrial function and aging processes...
2017: Frontiers in Molecular Neuroscience
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