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https://www.readbyqxmd.com/read/28445974/lowered-expression-of-microrna-125a-5p-in-human-hepatocellular-carcinoma-and-up-regulation-of-its-oncogenic-targets-sirtuin-7-matrix-metalloproteinase-11-and-c-raf
#1
Nicola Coppola, Giorgio de Stefano, Marta Panella, Lorenzo Onorato, Valentina Iodice, Carmine Minichini, Nicola Mosca, Luisa Desiato, Nunzia Farella, Mario Starace, Giulia Liorre, Nicoletta Potenza, Evangelista Sagnelli, Aniello Russo
Human microRNA-125a-5p (miR-125a) is expressed in most tissues where it downregulates the expression of membrane receptors or intracellular transductors of mitogenic signals, thus limiting cell proliferation. Expression of this miRNA generally increases with cell differentiation whereas it is downregulated in several types of tumors, such as breast, lung, ovarian, gastric, colon, and cervical cancers, neuroblastoma, medulloblastoma, glioblastoma, and retinoblastoma. In this study, we focused on hepatocellular carcinoma and used real-time quantitative PCR to measure miR-125a expression in 55 tumor biopsies and in matched adjacent non-tumor liver tissues...
April 11, 2017: Oncotarget
https://www.readbyqxmd.com/read/28445726/sirtuin-1-activation-controls-tumor-growth-by-impeding-th17-differentiation-via-stat3-deacetylation
#2
Emeric Limagne, Marion Thibaudin, Romain Euvrard, Hélène Berger, Pauline Chalons, Frédérique Végan, Etienne Humblin, Romain Boidot, Cédric Rébé, Valentin Derangère, Sylvain Ladoire, Lionel Apetoh, Dominique Delmas, François Ghiringhelli
Sirtuin-1 deacetylates proteins and has emerged as a critical regulator of different cellular processes, particularly inflammation. Basal SIRT1 activity was previously found to limit Th9 and enhance Th17 differentiation in mice, but the effect of pharmacological SIRT1 activation on T cell differentiation and antitumor responses remains unclear. Here, we find that SIRT1 pharmacological agonists selectively impede mouse and human Th17 cell differentiation. SIRT1 activation induces STAT3 deacetylation, thus reducing its ability to translocate into the nucleus, bind to Rorc promoter, and induce its transcription...
April 25, 2017: Cell Reports
https://www.readbyqxmd.com/read/28445509/functional-genetic-variants-within-the-sirt2-gene-promoter-in-acute-myocardial-infarction
#3
Wentao Yang, Feng Gao, Pei Zhang, Shuchao Pang, Yinghua Cui, Lixin Liu, Guanghe Wei, Bo Yan
Coronary artery disease (CAD), including acute myocardial infarction (AMI) is the complication of atherosclerosis. Recently, genome-wide association studies have identified a large number of CAD-related genetic variants. However, only 10% of CAD cases could be explained. Low frequent and rare genetic variants have been recently proposed to be main causes for CAD. SIRT2 is a member of sirtuin family, NAD(+)-dependent class III deacetylases. SIRT2 is involved in genomic stability, metabolism, inflammation, oxidative stress and autophagy, as well as in platelet function...
2017: PloS One
https://www.readbyqxmd.com/read/28440450/comprehensive-analysis-of-a-microrna-expression-profile-in-pediatric-medulloblastoma
#4
Junqiang Dai, Qiao Li, Zhitong Bing, Yinian Zhang, Liang Niu, Hang Yin, Guoqiang Yuan, Yawen Pan
Medulloblastoma is the most common malignant brain tumor of the central nervous system among children. Medulloblastoma is an embryonal tumor, of which little is known about the pathogenesis. Several efforts have been made to understand the molecular aspects of its tumorigenic pathways; however, these are poorly understood. microRNA (miRNA), a type of non‑coding short RNA, has been proven to be associated with a number of physiological processes and pathological processes of serious diseases, including brain tumors...
April 20, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28439035/the-regulation-function-and-detection-of-protein-acetylation-in-bacteria
#5
Valerie J Carabetta, Ileana M Cristea
N(ε)-lysine acetylation is now recognized as an abundant post-translational modification (PTM) that influences many essential biological pathways. Advancements in mass spectrometry-based proteomics have led to the discovery that bacteria contain hundreds of acetylated proteins, contrary to the prior notion of rare acetylation events in bacteria. Although the mechanisms that regulate protein acetylation are still not fully defined, it is understood that this modification is finely-tuned via both enzymatic and non-enzymatic mechanisms...
April 24, 2017: Journal of Bacteriology
https://www.readbyqxmd.com/read/28436940/disruption-of-spatiotemporal-hypoxic-signaling-causes-congenital-heart-disease-in-mice
#6
Xuejun Yuan, Hui Qi, Xiang Li, Fan Wu, Jian Fang, Eva Bober, Gergana Dobreva, Yonggang Zhou, Thomas Braun
Congenital heart disease (CHD) represents the most prevalent inborn anomaly. Only a minority of CHD cases are attributed to genetic causes, suggesting a major role of environmental factors. Nonphysiological hypoxia during early pregnancy induces CHD, but the underlying reasons are unknown. Here, we have demonstrated that cells in the mouse heart tube are hypoxic, while cardiac progenitor cells (CPCs) expressing islet 1 (ISL1) in the secondary heart field (SHF) are normoxic. In ISL1+ CPCs, induction of hypoxic responses caused CHD by repressing Isl1 and activating NK2 homeobox 5 (Nkx2...
April 24, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28435470/downregulation-of-sirt7-by-5-fluorouracil-induces-radiosensitivity-in-human-colorectal-cancer
#7
Ming Tang, Xiaopeng Lu, Chaohua Zhang, Changzheng Du, Linlin Cao, Tianyun Hou, Zhiming Li, Bo Tu, Ziyang Cao, Yinglu Li, Yongcan Chen, Lu Jiang, Hui Wang, Lina Wang, Baohua Liu, Xingzhi Xu, Jianyuan Luo, Jiadong Wang, Jin Gu, Haiying Wang, Wei-Guo Zhu
5-Fluorouracil (5-FU) combined with radiotherapy is a common treatment strategy to treat human cancers, but the underlying mechanisms of this combination treatment remain unclear. Here, we report that NAD(+)-dependent deacetylase sirtuin-7 (SIRT7) protein levels were decreased due to 5-FU exposure rendering colorectal cancer cells sensitive to radiation. We found that SIRT7 downregulation was mediated via a Tat-binding Protein 1 (TBP1) proteasome-dependent pathway. Specifically, TBP1 was dephosphorylated at tyrosine 381 upon 5-FU treatment, which enhanced its direct interaction with SIRT7 and targeted it for degradation...
2017: Theranostics
https://www.readbyqxmd.com/read/28433634/dual-sphingosine-kinase-inhibitor-ski-ii-enhances-sensitivity-to-5-fluorouracil-in-hepatocellular-carcinoma-cells-via-suppression-of-osteopontin-and-fak-igf-1r-signalling
#8
Petra Grbčić, Ivana Tomljanović, Marko Klobučar, Sandra Kraljević Pavelić, Ksenija Lučin, Mirela Sedić
Hepatocellular carcinoma (HCC) represents the third leading cause of cancer-related deaths globally. Although 5-Fluorouracil (5-FU) is used as the first choice treatment for advanced HCC, it exerts poor efficacy and is associated with acquired and intrinsic resistance. Sphingosine kinases (Sphk) 1 and 2 play tumour-promoting roles in different cancer types including HCC and thus represent promising pharmacological targets. In the present study, we have investigated for the first time the anticancer efficacy and underlying molecular mechanisms of combined administration of 5-FU and dual Sphk1/Sphk2 inhibitor SKI-II (4-[[4-(4-chlorophenyl)-1,3-thiazol-2-yl]amino]phenol) in HepG2 hepatocellular carcinoma cells...
April 19, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28433458/linking-the-biological-underpinnings-of-depression-role-of-mitochondria-interactions-with-melatonin-inflammation-sirtuins-tryptophan-catabolites-dna-repair-and-oxidative-and-nitrosative-stress-with-consequences-for-classification-and-cognition
#9
REVIEW
George Anderson
The pathophysiological underpinnings of neuroprogressive processes in recurrent major depressive disorder (rMDD) are reviewed. A wide array of biochemical processes underlie MDD presentations and their shift to a recurrent, neuroprogressive course, including: increased immune-inflammation, tryptophan catabolites (TRYCATs), mitochondrial dysfunction, aryl hydrocarbonn receptor activation, and oxidative and nitrosative stress (O&NS), as well as decreased sirtuins and melatonergic pathway activity. These biochemical changes may have their roots in central, systemic and/or peripheral sites, including in the gut, as well as in developmental processes, such as prenatal stressors and breastfeeding consequences...
April 19, 2017: Progress in Neuro-psychopharmacology & Biological Psychiatry
https://www.readbyqxmd.com/read/28429797/sirtuins-in-the-phylum-basidiomycota-a-role-in-virulence-in-cryptococcus-neoformans
#10
Samantha D M Arras, Jessica L Chitty, Maha S I Wizrah, Paige E Erpf, Benjamin L Schulz, Milos Tanurdzic, James A Fraser
Virulence of Cryptococcus neoformans is regulated by a range of transcription factors, and is also influenced by the acquisition of adaptive mutations during infection. Beyond the temporal regulation of virulence factor production by transcription factors and these permanent microevolutionary changes, heritable epigenetic modifications such as histone deacetylation may also play a role during infection. Here we describe the first comprehensive analysis of the sirtuin class of NAD+ dependent histone deacetylases in the phylum Basidiomycota, identifying five sirtuins encoded in the C...
April 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28429673/hydroxytyrosol-attenuates-lps-induced-acute-lung-injury-in-mice-by-regulating-autophagy-and-sirtuin-expression
#11
X Yang, T Jing, Y Li, Y He, B Wang, W Zhang, Y Xiao, W Wang, J Zhang, J Wei, R Lin
BACKGROUND: Recently, the effects of hydroxytyrosol on autophagy during acute lung injury (ALI) have drawn increasing attention. OBJECTIVE: We explored the underlying molecular mechanisms by which hydroxytyrosol exerts its anti-inflammatory effects in a murine model of ALI by up-regulating autophagy. METHODS: Male BALB/c mice, challenged with intranasal instillations of LPS, were treated with or without hydroxytyrosol (HT, 100 mg/kg, intragastrically) 1 h prior to LPS exposure...
April 21, 2017: Current Molecular Medicine
https://www.readbyqxmd.com/read/28427524/kallistatin-suppresses-cancer-development-by-multi-factorial-actions
#12
REVIEW
Julie Chao, Pengfei Li, Lee Chao
Kallistatin was first identified in human plasma as a tissue kallikrein-binding protein and a serine proteinase inhibitor. Kallistatin via its two structural elements regulates differential signaling cascades, and thus a wide spectrum of biological functions. Kallistatin's active site is essential for: inhibiting tissue kallikrein's activity; stimulating endothelial nitric oxide synthase and sirtuin 1 expression and activation; and modulating the synthesis of the microRNAs, miR-34a, miR-21 and miR-203. Kallistatin's heparin-binding site is crucial for antagonizing the signaling pathways of vascular endothelial growth factor, tumor necrosis factor-α, Wnt, transforming growth factor-β and epidermal growth factor...
May 2017: Critical Reviews in Oncology/hematology
https://www.readbyqxmd.com/read/28425936/genistein-ameliorates-ischemia-reperfusion-induced-renal-injury-in-a-sirt1-dependent-manner
#13
Wei-Fang Li, Kang Yang, Ping Zhu, Hong-Qian Zhao, Yin-Hong Song, Kuan-Can Liu, Wei-Feng Huang
Renal ischemia/reperfusion (I/R) injury continues to be a complicated situation in clinical practice. Genistein, the main isoflavone found in soy products, is known to possess a wide spectrum of biochemical and pharmacological activities. However, the protective effect of genistein on renal I/R injury has not been well investigated. In the current study, we explore whether genistein exhibits its renal-protective effects through SIRT1 (Sirtuin 1) in I/R-induced mice model. We found the treatment of genistein significantly reduced renal I/R-induced cell death, simultaneously stimulating renal cell proliferation...
April 20, 2017: Nutrients
https://www.readbyqxmd.com/read/28424621/activation-of-sirtuin-3-by-silybin-attenuates-mitochondrial-dysfunction-in-cisplatin-induced-acute-kidney-injury
#14
Yin Li, Zengchun Ye, Weiyan Lai, Jialing Rao, Wanbing Huang, Xiaohao Zhang, Ziying Yao, Tanqi Lou
Silybin is a secondary metabolite isolated from the seeds of blessed milk thistle (Silybum marianum) that has anti-inflammatory, antioxidative, antifibrotic, and antitumor properties. Here, we showed that silybin protected against cisplatin-induced acute kidney injury (AKI) by improving mitochondrial function through the regulation of sirtuin 3 (SIRT3) expression. Male SV129 and SIRT3 knockout (KO) mice were administered a single intraperitoneal (i.p.) injection of cisplatin with or without treatment with silybin...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28424160/heterogeneous-nuclear-ribonucleoprotein-f-stimulates-sirtuin-1-gene-expression-and-attenuates-nephropathy-progression-in-diabetic-mice
#15
Chao-Sheng Lo, Yixuan Shi, Isabelle Chenier, Anindya Ghosh, Chin-Han Wu, Jean-Francois Cailhier, Jean Ethier, Jean-Baptiste Lattouf, Janos G Filep, Julie R Ingelfinger, Shao-Ling Zhang, John S D Chan
We investigated the mechanism of heterogeneous nuclear ribonucleoprotein F (hnRNP F) renoprotective action on a type 2 diabetic (T2D) (db/db) mice. Immortalized rat renal proximal tubular cells (IRPTCs) and human T2D kidneys were also studied. Db/db mice developed hyperglycemia, oxidative stress and nephropathy at age 20 weeks compared to their db/m littermates. These abnormalities, with the exception of hyperglycemia, were attenuated in db/db hnRNP F-transgenic (Tg) mice specifically overexpressing hnRNP F in their RPTCs...
April 19, 2017: Diabetes
https://www.readbyqxmd.com/read/28423723/honokiol-an-activator-of-sirtuin-3-sirt3-preserves-mitochondria-and-protects-the-heart-from-doxorubicin-induced-cardiomyopathy-in-mice
#16
Vinodkumar B Pillai, Abhinav Kanwal, Yong Hu Fang, Willard W Sharp, Sadhana Samant, Jack Arbiser, Mahesh P Gupta
Doxorubicin is the chemotherapeutic drug of choice for a wide variety of cancers, and cardiotoxicity is one of the major side effects of doxorubicin treatment. One of the main cellular targets of doxorubicin in the heart is mitochondria. Mitochondrial sirtuin, SIRT3 has been shown to protect against doxorubicin-induced cardiotoxicity. We have recently identified honokiol (HKL) as an activator of SIRT3, which protects the heart from developing pressure overload hypertrophy. Here, we show that HKL-mediated activation of SIRT3 also protects the heart from doxorubicin-induced cardiac damage without compromising the tumor killing potential of doxorubicin...
March 11, 2017: Oncotarget
https://www.readbyqxmd.com/read/28420170/fisetin-protects-pc12-cells-from-tunicamycin-mediated-cell-death-via-reactive-oxygen-species-scavenging-and-modulation-of-nrf2-driven-gene-expression-sirt1-and-mapk-signaling-in-pc12-cells
#17
Jui-Hung Yen, Pei-Shan Wu, Shu-Fen Chen, Ming-Jiuan Wu
BACKGROUND: Fisetin (3,7,3',4'-tetrahydroxyflavone) is a dietary flavonol and exhibits antioxidant, anti-inflammatory, and neuroprotective activities. However, high concentration of fisetin is reported to produce reactive oxygen species (ROS), induce endoplasmic reticulum (ER) stress and cause cytotoxicity in cancer cells. The aim of this study is to investigate the cytoprotective effects of low concentration of fisetin against tunicamycin (Tm)-mediated cytotoxicity in neuronal-like catecholaminergic PC12 cells...
April 17, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28419207/ckii-sirt1-sm22%C3%AE-loop-evokes-a-self-limited-inflammatory-response-in-vascular-smooth-muscle-cells
#18
Ya-Nan Shu, Li-Hua Dong, Han Li, Qian-Qian Pei, Sui-Bing Miao, Fan Zhang, Dan-Dan Zhang, Rong Chen, Ya-Juan Yin, Yan-Ling Lin, Zhen-Ying Xue, Pin Lv, Xiao-Li Xie, Li-Li Zhao, Xi Nie, Peng Chen, Mei Han
Aims: Sirtuin 1 (SIRT1) inhibits nuclear factor kappa B (NF-κB) activity in response to the inflammatory cytokine tumour necrosis factor alpha (TNF-α). Smooth muscle (SM) 22α is a phosphorylation-regulated suppressor of IKK-IκBα-NF-κB signalling cascades in vascular smooth muscle cells (VSMCs). Sm22α knockout results in increased expression of pro-inflammatory genes in the aortas which are controlled by NF-κB. This study aimed to investigate the relationship between SM22α and SIRT1 in the control of vascular inflammation...
April 16, 2017: Cardiovascular Research
https://www.readbyqxmd.com/read/28417539/usp22-mediates-the-multidrug-resistance-of-hepatocellular-carcinoma-via-the-sirt1-akt-mrp1-signaling-pathway
#19
Sunbin Ling, Jie Li, Qiaonan Shan, Haojiang Dai, Di Lu, Xue Wen, Penghong Song, Haiyang Xie, Lin Zhou, Jimin Liu, Xiao Xu, Shusen Zheng
Drug treatments for hepatocellular carcinoma (HCC) often fail because of multidrug resistance (MDR). The mechanisms of MDR are complex but cancer stem cells (CSC), which are able to self-renew and differentiate, have recently been shown to be involved. The deubiquitinating enzyme ubiquitin-specific protease 22 (USP22) is a marker for CSCs. This study aimed to elucidate the role of USP22 in MDR of HCC and the underlying mechanisms. Using in vitro and in vivo assays, we found that modified USP22 levels were responsible for the altered drug-resistant phenotype of BEL7402 and BEL/FU cells...
April 18, 2017: Molecular Oncology
https://www.readbyqxmd.com/read/28417163/nicotinamide-is-an-inhibitor-of-sirt1-in-vitro-but-can-be-a-stimulator-in-cells
#20
REVIEW
Eun Seong Hwang, Seon Beom Song
Nicotinamide (NAM), a form of vitamin B3, plays essential roles in cell physiology through facilitating NAD(+) redox homeostasis and providing NAD(+) as a substrate to a class of enzymes that catalyze non-redox reactions. These non-redox enzymes include the sirtuin family proteins which deacetylate target proteins while cleaving NAD(+) to yield NAM. Since the finding that NAM exerts feedback inhibition to the sirtuin reactions, NAM has been widely used as an inhibitor in the studies where SIRT1, a key member of sirtuins, may have a role in certain cell physiology...
April 17, 2017: Cellular and Molecular Life Sciences: CMLS
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