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https://www.readbyqxmd.com/read/29325994/the-effects-of-melatonin-and-curcumin-on-the-expression-of-sirt2-bcl-2-and-bax-in-the-hippocampus-of-adult-rats
#1
Arzu Keskin-Aktan, Kazime Gonca Akbulut, Çiğdem Yazici-Mutlu, Gizem Sonugur, Müge Ocal, Hakan Akbulut
OBJECTIVE: Though the mechanisms are not clearly understood, melatonin and curcumin have been reported to have neuroprotective effects. However, the mechanisms of neuroprotective effects of melatonin and curcumin in the brain are not clearly understood. In the current study, we investigated the effects of melatonin and curcumin treatments on oxidative stress parameters, the expression of SIRT2, Bcl-2 and Bax in the hippocampus. METHODS: A total of twenty-four adult (13 months-old) male Wistar rats were divided into four groups: Control (1% ethanol:PBS), s...
January 8, 2018: Brain Research Bulletin
https://www.readbyqxmd.com/read/29304479/microrna-140-5p-aggravates-doxorubicin-induced-cardiotoxicity-by-promoting-myocardial-oxidative-stress-via-targeting-nrf2-and-sirt2
#2
Lisha Zhao, Yan Qi, Lina Xu, Xufeng Tao, Xu Han, Lianhong Yin, Jinyong Peng
Clinical application of doxorubicin (DOX), an anthracycline antibiotic with potent anti- tumor effects, is limited because of its cardiotoxicity. However, its pathogenesis is still not entirely understood. The aim of this paper was to explore the mechanisms and new drug targets to treat DOX-induced cardiotoxicity. The in vitro model on H9C2 cells and the in vivo models on rats and mice were developed. The results showed that DOX markedly decreased H9C2 cell viability, increased the levels of CK, LDH, caused histopathological and ECG changes in rats and mice, and triggered myocardial oxidative damage via adjusting the levels of intracellular ROS, MDA, SOD, GSH and GSH-Px...
December 29, 2017: Redox Biology
https://www.readbyqxmd.com/read/29298345/redox-modulation-of-nqo1
#3
David Siegel, Donna D Dehn, Samantha S Bokatzian, Kevin Quinn, Donald S Backos, Andrea Di Francesco, Michel Bernier, Nichole Reisdorph, Rafael de Cabo, David Ross
NQO1 is a FAD containing NAD(P)H-dependent oxidoreductase that catalyzes the reduction of quinones and related substrates. In cells, NQO1 participates in a number of binding interactions with other proteins and mRNA and these interactions may be influenced by the concentrations of reduced pyridine nucleotides. NAD(P)H can protect NQO1 from proteolytic digestion suggesting that binding of reduced pyridine nucleotides results in a change in NQO1 structure. We have used purified NQO1 to demonstrate the addition of NAD(P)H induces a change in the structure of NQO1; this results in the loss of immunoreactivity to antibodies that bind to the C-terminal domain and to helix 7 of the catalytic core domain...
2018: PloS One
https://www.readbyqxmd.com/read/29296001/sirt2-facilitates-hepatic-glucose-uptake-by-deacetylating-glucokinase-regulatory-protein
#4
Hitoshi Watanabe, Yuka Inaba, Kumi Kimura, Michihiro Matsumoto, Shuichi Kaneko, Masato Kasuga, Hiroshi Inoue
Impaired hepatic glucose uptake (HGU) causes postprandial hyperglycemia in type 2 diabetes. Here, we show that diminished hepatic Sirt2 activity impairs HGU in obese diabetic mice. Hepatic Sirt2 overexpression increases HGU in high-fat diet (HFD)-fed obese diabetic mice and mitigates their impaired glucose tolerance. Hepatic Sirt2 knockdown in non-diabetic mice reduces HGU and causes impaired glucose tolerance. Sirt2 promotes glucose-dependent HGU by deacetylating K126 of glucokinase regulatory protein (GKRP)...
January 2, 2018: Nature Communications
https://www.readbyqxmd.com/read/29249955/expression-of-sirtuins-in-the-retinal-neurons-of-mice-rats-and-humans
#5
Hongdou Luo, Min Zhou, Kaibao Ji, Jiejie Zhuang, Wenjie Dang, Shiya Fu, Tao Sun, Xu Zhang
Sirtuins are a class of histone deacetylases (HDACs) that have been shown to regulate a range of pathophysiological processes such as cellular aging, inflammation, metabolism, and cell proliferation. There are seven mammalian Sirtuins (SIRT1-7) that play important roles in stress response, aging, and neurodegenerative diseases. However, the location and function of Sirtuins in neurons are not well defined. This study assessed the retinal expression of Sirtuins in mice, rats, and humans and measured the expression of Sirtuins in aged and injured retinas...
2017: Frontiers in Aging Neuroscience
https://www.readbyqxmd.com/read/29239724/sirt2-and-lysine-fatty-acylation-regulate-the-transforming-activity-of-k-ras4a
#6
Hui Jing, Xiaoyu Zhang, Stephanie A Wisner, Xiao Chen, Nicole A Spiegelman, Maurine E Linder, Hening Lin
Ras proteins play vital roles in numerous biological processes and Ras mutations are found in many human tumors. Understanding how Ras proteins are regulated is important for elucidating cell signaling pathways and identifying new targets for treating human diseases. Here we report that one of the K-Ras splice variants, K-Ras4a, is subject to lysine fatty acylation, a previously under-studied protein post-translational modification. Sirtuin 2 (SIRT2), one of the mammalian nicotinamide adenine dinucleotide (NAD)-dependent lysine deacylases, catalyzes the removal of fatty acylation from K-Ras4a...
December 14, 2017: ELife
https://www.readbyqxmd.com/read/29222643/overexpression-of-sirt2-alleviates-neuropathic-pain-and-neuroinflammation-through-deacetylation-of-transcription-factor-nuclear-factor-kappa-b
#7
Yong Zhang, Dachao Chi
Sirtuin 2 (SIRT2), a member of the mammalian sirtuin family, plays an important role in the pathogenesis of various neurological diseases. However, whether SIRT2 is involved in the regulation of neuropathic pain remains unclear. In this study, we aimed to investigate the potential role of SIRT2 in regulating neuropathic pain in a rat model induced by chronic constriction injury (CCI). We found that SIRT2 was downregulated in the dorsal root ganglion (DRG) in CCI rats. Intrathecal injection of a recombinant adenovirus expressing SIRT2 markedly alleviated mechanical allodynia and thermal hyperalgesia in CCI rats...
December 8, 2017: Inflammation
https://www.readbyqxmd.com/read/29213065/modulation-of-microtubule-acetylation-by-the-interplay-of-tppp-p25-sirt2-and-new-anticancer-agents-with-anti-sirt2-potency
#8
Adél Szabó, Judit Oláh, Sándor Szunyogh, Attila Lehotzky, Tibor Szénási, Marianna Csaplár, Matthias Schiedel, Péter Lőw, Manfred Jung, Judit Ovádi
The microtubule network exerts multifarious functions controlled by its decoration with various proteins and post-translational modifications. The disordered microtubule associated Tubulin Polymerization Promoting Protein (TPPP/p25) and the NAD+-dependent tubulin deacetylase sirtuin-2 (SIRT2) play key roles in oligodendrocyte differentiation by acting as dominant factors in the organization of myelin proteome. Herein, we show that SIRT2 impedes the TPPP/p25-promoted microtubule assembly independently of NAD+; however, the TPPP/p25-assembled tubulin ultrastructures were resistant against SIRT2 activity...
December 6, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29189925/overexpression-of-sirtuin2-prevents-high-glucose-induced-vascular-endothelial-cell-injury-by-regulating-the-p53-and-nf-%C3%AE%C2%BAb-signaling-pathways
#9
Wenguang Zhang, Dongmei Liu, Jianzhuang Ren, Pengli Zhou, Xinwei Han
OBJECTIVES: To investigate the potential role and underlying mechanism of Sirtuin2 (SIRT2) in regulating high glucose (HG)-induced vascular endothelial cell injury by using human umbilical vein endothelial cells (HUVECs). RESULTS: SIRT2 mRNA and protein expression levels were decreased in HG-treated HUVECs. SIRT2 overexpression increased viability, decreased apoptosis and reduced levels of reactive oxygen species in HG-treated HUVECs. SIRT2 overexpression decreased TNF-α expression (146...
November 30, 2017: Biotechnology Letters
https://www.readbyqxmd.com/read/29189472/sirt2-and-akt-mediate-nad-induced-and-nadh-induced-increases-in-the-intracellular-atp-levels-of-bv2-microglia-under-basal-conditions
#10
Jie Zhang, Caixia Wang, Weihai Ying
NAD replenishment can restore ATP levels and rescue premature aging in Cockayne syndrome mice. However, there has been no mechanistic study regarding the effects of NAD and NADH on intracellular ATP levels under basal conditions. In our current study, we used BV2 microglia to test our hypothesis that NAD and NADH can increase intracellular ATP levels under basal conditions. We found that both NAD and NADH significantly increased the intracellular ATP levels of BV2 microglia, which were attenuated by SIRT2 siRNA, the SIRT2 inhibitor AGK2, and the phosphatidylinositol 3-kinase/Akt inhibitor LY294002...
November 20, 2017: Neuroreport
https://www.readbyqxmd.com/read/29158185/cdk5-mediated-phosphorylation-of-sirt2-contributes-to-depressive-like-behavior-induced-by-social-defeat-stress
#11
Zheng Zhang, Pei Zhang, Guang-Jian Qi, Feng-Juan Jiao, Qing-Zhi Wang, Jian-Guo Yan, Feng He, Qian Zhang, Ze-Xi Lv, Xiang Peng, Hong-Wei Cai, Xiaoqian Chen, Ning Sun, Bo Tian
Major depressive disorder (MDD) is a common, severe and recurrent psychiatric disorder worldwide; however, the underlying neuropathological mechanisms remain elusive. Histone deacetylases (HDACs) appear to play an essential role in depression. As the class III HDACs, Sirt1 and Sirt2 have attracted the most interest in the nervous system. Indeed, chronic stress decreased Sirt1 activity and down-regulated Sirt1 gene expression in MDD. Nevertheless, there is a paucity of literature on the role of Sirt2. To study the role of Sirt2 we established a MDD mouse model in wild type and Sirt2 knockout C57BL/6 mice using social defeat stress (SDS)...
November 17, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29150224/reduced-gene-expression-of-sirtuins-and-active-ampk-levels-in-children-and-adolescents-with-obesity-and-insulin-resistance
#12
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/29145149/sirt2-decreases-atherosclerotic-plaque-formation-in-low-density-lipoprotein-receptor-deficient-mice-by-modulating-macrophage-polarization
#13
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/29132743/nuclear-sirtuins-and-inflammatory-signaling-pathways
#14
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/29125735/resveratrol-exerts-antioxidant-effects-by-activating-sirt2-to-deacetylate-prx1
#15
Yanchao Pan, Hua Zhang, Yueting Zheng, Juanzuo Zhou, Jing Yuan, Yang Yu, Jiangyun Wang
Resveratrol is a promising chemical agent that treats multiple aging-related diseases and improves healthspan. While reactive oxygen species (ROS) undoubtedly play ubiquitous roles in the aging process and resveratrol has been shown to be an effective antioxidant, the mechanism through which resveratrol acts against oxidative stress remains unknown. Here we show that resveratrol activates Sirt2 to deacetylate Prx1, leading to increased H2O2 reduction activity and decreased cellular H2O2 concentration. Knockdown of Sirt2 or Prx1 by RNA interference abrogates resveratrol's ability to reduce H2O2 level in HepG2 cells...
November 10, 2017: Biochemistry
https://www.readbyqxmd.com/read/29067790/sirt2-bubr1-acetylation-pathway-mediates-the-effects-of-advanced-maternal-age-on-oocyte-quality
#16
Danhong Qiu, Xiaojing Hou, Longsen Han, Xiaoyan Li, Juan Ge, Qiang Wang
The level of Sirt2 protein is reduced in oocytes from aged mice, while exogenous expression of Sirt2 could ameliorate the maternal age-associated meiotic defects. To date, the underlying mechanism remains unclear. Here, we confirmed that specific depletion of Sirt2 disrupts maturational progression and spindle/chromosome organization in mouse oocytes, with compromised kinetochore-microtubule attachments. Candidate screening revealed that acetylation state of lysine 243 on BubR1 (BubR1-K243, an integral part of the spindle assembly checkpoint complex) functions during oocyte meiosis, and acetylation-mimetic mutant BubR1-K243Q results in the very similar phenotypes as Sirt2-knockdown oocytes...
October 25, 2017: Aging Cell
https://www.readbyqxmd.com/read/29034508/ulk4-deficiency-leads-to-hypomyelination-in-mice
#17
Min Liu, Ping Xu, Zhenlong Guan, Xiaohong Qian, Peter Dockery, Una Fitzgerald, Timothy O'Brien, Sanbing Shen
Brain nerve fibers are insulated by myelin which is produced by oligodendrocytes. Defects in myelination are increasingly recognized as a common pathology underlying neuropsychiatric and neurodevelopmental disorders, which are associated with deletions of the Unc-51-like kinase 4 (ULK4) gene. Key transcription factors have been identified for oligodendrogenesis, but little is known about their associated regulators. Here we report that Ulk4 acts as a key regulator of myelination. Myelination is reduced by half in the Ulk4(tm1a/tm1a) hypomorph brain, whereas expression of axonal marker genes Tubb3, Nefh, Nefl and Nefm remains unaltered...
January 2018: Glia
https://www.readbyqxmd.com/read/28992545/downregulation-of-sirt2-inhibits-invasion-of-hepatocellular-carcinoma-by-inhibiting-energy-metabolism
#18
Shan Huang, Zhenguo Zhao, Dehua Tang, Qian Zhou, Yang Li, Lixing Zhou, Yuyao Yin, Yuming Wang, Yida Pan, Robert Gregory Dorfman, Tingsheng Ling, Mingming Zhang
Hepatocellular carcinoma (HCC) is one of the most common neoplasms, and metastasis is the most important feature for HCC-related deaths. Mounting evidence implies the dynamic regulatory role of SIRT2, a histone deacetylase, in cancer cells. Unfortunately, the role of SIRT2 and the antitumor activity of its inhibition are not known in HCC. The present study aims to evaluate the biological function of SIRT2 in HCC and identify the target of SIRT2 as well as evaluate its therapeutic efficacy. We found that SIRT2 was upregulated in HCC tissues compared to adjacent normal tissues, and this was correlated with reduced patient survival...
December 2017: Translational Oncology
https://www.readbyqxmd.com/read/28989670/potent-mechanism-based-sirtuin-2-selective-inhibition-by-an-in-situ-generated-occupant-of-the-substrate-binding-site-selectivity-pocket-and-nad-binding-site
#19
Paolo Mellini, Yukihiro Itoh, Hiroki Tsumoto, Ying Li, Miki Suzuki, Natsuko Tokuda, Taeko Kakizawa, Yuri Miura, Jun Takeuchi, Maija Lahtela-Kakkonen, Takayoshi Suzuki
Sirtuin 2 (SIRT2), a member of the NAD(+)-dependent histone deacetylase family, has recently received increasing attention due to its potential involvement in neurodegenerative diseases and the progression of cancer. Potent and selective SIRT2 inhibitors thus represent desirable biological probes. Based on the X-ray crystal structure of SIRT2 in complex with a previously reported weak inhibitor (6), we identified in this study the potent mechanism-based inactivator KPM-2 (36), which is selective toward SIRT2...
September 1, 2017: Chemical Science
https://www.readbyqxmd.com/read/28984064/loss-of-sirt2-leads-to-axonal-degeneration-and-locomotor-disability-associated-with-redox-and-energy-imbalance
#20
Stéphane Fourcade, Laia Morató, Janani Parameswaran, Montserrat Ruiz, Tatiana Ruiz-Cortés, Mariona Jové, Alba Naudí, Paloma Martínez-Redondo, Mara Dierssen, Isidre Ferrer, Francesc Villarroya, Reinald Pamplona, Alejandro Vaquero, Manel Portero-Otín, Aurora Pujol
Sirtuin 2 (SIRT2) is a member of a family of NAD(+) -dependent histone deacetylases (HDAC) that play diverse roles in cellular metabolism and especially for aging process. SIRT2 is located in the nucleus, cytoplasm, and mitochondria, is highly expressed in the central nervous system (CNS), and has been reported to regulate a variety of processes including oxidative stress, genome integrity, and myelination. However, little is known about the role of SIRT2 in the nervous system specifically during aging. Here, we show that middle-aged, 13-month-old mice lacking SIRT2 exhibit locomotor dysfunction due to axonal degeneration, which was not present in young SIRT2 mice...
December 2017: Aging Cell
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