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https://www.readbyqxmd.com/read/28804553/sirt3-attenuates-doxorubicin-induced-cardiac-hypertrophy-and-mitochondrial-dysfunction-via-suppression-of-bnip3
#1
Qiong Du, Bin Zhu, Qing Zhai, Bo Yu
Doxorubicin (Dox) is an anthracycline antibiotic widely used in cancer treatment. Although its antitumor efficacy appears to be dose dependent, its clinical use is greatly restricted by development of cardiotoxicity. Sirtuin-3 (Sirt3) is the major deacetylase within the mitochondrial matrix that plays an important role in regulation of cardiac function. This study was performed to identify the regulatory role of Sirt3 on Dox-induced cardiac hypertrophy and mitochondrial dysfunction in rats in vivo and in vitro...
2017: American Journal of Translational Research
https://www.readbyqxmd.com/read/28798665/maternal-diabetes-alters-expression-of-micrornas-that-regulate-genes-critical-for-neural-tube-development
#2
Seshadri Ramya, Sukanya Shyamasundar, Boon Huat Bay, S Thameem Dheen
Maternal diabetes is known to cause neural tube defects (NTDs) in embryos and neuropsychological deficits in infants. Several metabolic pathways and a plethora of genes have been identified to be deregulated in developing brain of embryos by maternal diabetes, although the exact mechanism remains unknown. Recently, miRNAs have been shown to regulate genes involved in brain development and maturation. Therefore, we hypothesized that maternal diabetes alters the expression of miRNAs that regulate genes involved in biological pathways critical for neural tube development and closure during embryogenesis...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28793258/crucial-roles-for-sirt2-and-ampa-receptor-acetylation-in-synaptic-plasticity-and-memory
#3
Guan Wang, Shaomin Li, James Gilbert, Howard J Gritton, Zemin Wang, Zhangyuan Li, Xue Han, Dennis J Selkoe, Heng-Ye Man
AMPA receptors (AMPARs) mediate fast excitatory synaptic transmission and are crucial for synaptic plasticity, learning, and memory. However, the molecular control of AMPAR stability and its neurophysiological significance remain unclear. Here, we report that AMPARs are subject to lysine acetylation at their C termini. Acetylation reduces AMPAR internalization and degradation, leading to increased cell-surface localization and prolonged receptor half-life. Through competition for the same lysine residues, acetylation intensity is inversely related to the levels of AMPAR ubiquitination...
August 8, 2017: Cell Reports
https://www.readbyqxmd.com/read/28789977/ablation-of-systemic-sirt1-activity-promotes-nonalcoholic-fatty-liver-disease-by-affecting-liver-mesenteric-adipose-tissue-fatty-acid-mobilization
#4
Junrui Cheng, Chun Liu, Kangquan Hu, Andrew Greenberg, Dayong Wu, Lynne M Ausman, Michael W McBurney, Xiang-Dong Wang
Sirtuin 1 (SIRT1) has been reported to protect against nonalcoholic fatty liver disease (NAFLD) development. The mechanism of how SIRT1 deacetylase activity affects NAFLD has not been well investigated. The current investigation addressed the causal effect of systemic SIRT1 activity on NAFLD development and the underlying mechanism involved in both liver and mesenteric adipose tissue (MAT). Both SIRT1 homozygous mice ablated the catalytic activity (sirt1(Y/Y)) and their corresponding wild type littermates (WT) were fed a high fat diet (HFD, 60% calories from fat) for 34weeks...
August 5, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28789901/sirtuins-epigenetics-and-longevity
#5
REVIEW
Mateusz Wątroba, Ilona Dudek, Marta Skoda, Aleksandra Stangret, Przemysław Rzodkiewicz, Dariusz Szukiewicz
Aging of organisms begins from a single cell at the molecular level. It includes changes related to telomere shortening, cell senescence and epigenetic modifications. These processes accumulate over the lifespan. Research studies show that epigenetic signaling contributes to human disease, tumorigenesis and aging. Epigenetic DNA modifications involve changes in the gene activity but not in the DNA sequence. An epigenome consists of chemical modifications to the DNA and histone proteins without the changes in the DNA sequence...
August 5, 2017: Ageing Research Reviews
https://www.readbyqxmd.com/read/28780164/changes-in-epigenetic-markers-dnmt1-and-hdac1-2-in-the-adult-mouse-hippocampus-after-cranial-irradiation
#6
Sohi Kang, Yeonghoon Son, Sueun Lee, Juhwan Kim, Jong-Choon Kim, Joong-Sun Kim, Uhee Jung, Sung-Ho Kim, Miyoung Yang, Changjong Moon
Brain exposure to ionizing radiation can cause functional deficits in the hippocampus, including memory impairment. However, the specific molecular mechanisms underlying irradiation-induced cognitive impairments are largely unknown. Changes in DNA methyltransferases (DNMTs) and histone deacetylases (HDACs), which are involved in DNA methylation and histone remodeling, may be associated with behavioral changes in learning and memory. We assessed changes in the levels of enzymes associated with the epigenetic modification of gene expression, including DNMT1, HDAC1, HDAC2, Sirtuin 1 (SIRT1), and acetylated histone H3 (Ace-H3) in the mouse hippocampus 1 and 30days after a single exposure to cranial irradiation (0 or 10Gy)...
August 2, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/28776959/development-of-substrate-derived-mechanistic-sirtuin-inhibitors-with-potential-anti-cancer-activity
#7
Michael Lammers, Nora Kuhlmann, Linda Baldus, Ines Neundorf, Constance Chollet
RhoGDIα is a key regulator for Rho-proteins coordinating their GTP/GDP- and membrane/cytosol-cycle. Recently, it was demonstrated by quantitative mass spectrometry that RhoGDIα is heavily targeted by post-translational lysine-acetylation. For one site in its N-terminal domain, namely K52, we reported that acetylation completely switches off RhoGDIα function. Here, we show that K52-acetylated RhoGDIα is specifically deacetylated by the sirtuin deacetylase Sirt2.. We show that acetylation at K52 decelerates cervical cancer cell proliferation, suggesting RhoGDIα acetylation to be a promising therapeutic target...
August 4, 2017: ChemMedChem
https://www.readbyqxmd.com/read/28774737/the-mechanism-of-diabetic-retinopathy-pathogenesis-unifying-key-lipid-regulators-sirtuin-1-and-liver-x-receptor
#8
Sandra S Hammer, Eleni Beli, Nermin Kady, Qi Wang, Kiana Wood, Todd A Lydic, Goldis Malek, Daniel R Saban, Xiaoxin X Wang, Sugata Hazra, Moshe Levi, Julia V Busik, Maria B Grant
Diabetic retinopathy (DR) is a complication secondary to diabetes and is the number one cause of blindness among working age individuals worldwide. Despite recent therapeutic breakthroughs using pharmacotherapy, a cure for DR has yet to be realized. Several clinical trials have highlighted the vital role dyslipidemia plays in the progression of DR. Additionally, it has recently been shown that activation of Liver X receptor (LXRα/LXRβ) prevents DR in diabetic animal models. LXRs are nuclear receptors that play key roles in regulating cholesterol metabolism, fatty acid metabolism and inflammation...
August 2017: EBioMedicine
https://www.readbyqxmd.com/read/28772080/hydroxytyrosol-regulates-the-autophagy-of-vascular-adventitial-fibroblasts-through-sirt1-mediated-signaling-pathway
#9
Weirong Wang, Ting Jing, Xiaofeng Yang, Yanhao He, Bo Wang, Yunfang Xiao, Chenxu Shang, Jiye Zhang, Rong Lin
Hydroxytyrosol (HT), a phenolic compound in olive oil, exerts anti-inflammatory effect in cardiovascular diseases. Recent studies found that autophagy was a therapeutic target of diseases. However, the effect of HT on autophagy in vascular adventitial fibroblasts (VAFs) remains unknown. Thus, in this study, we aimed to determine the effect of HT on cell autophagy and related signaling pathway, and whether HT regulates the inflammatory response through autophagy in VAFs. Our results showed that HT promoted cell autophagy by increasing the conversion of LC3 and Beclin1 expression and the autophagic flux in VAFs stimulated with TNF-α...
August 3, 2017: Canadian Journal of Physiology and Pharmacology
https://www.readbyqxmd.com/read/28768896/the-effects-of-graded-levels-of-calorie-restriction-xi-evaluation-of-the-main-hypotheses-underpinning-the-life-extension-effects-of-cr-using-the-hepatic-transcriptome
#10
Davina Derous, Sharon E Mitchell, Lu Wang, Cara L Green, Yingchun Wang, Luonan Chen, Jing-Dong J Han, Daniel E L Promislow, David Lusseau, Alex Douglas, John R Speakman
Calorie restriction (CR) may extend longevity by modulating the mechanisms involved in aging. Different hypotheses have been proposed for its main mode of action. We quantified hepatic transcripts of male C57BL/6 mice exposed to graded levels of CR (0% to 40% CR) for three months, and evaluated the responses relative to these various hypotheses. Of the four main signaling pathways implied to be linked to the impact of CR on lifespan (insulin/insulin like growth factor 1 (IGF-1), nuclear factor-kappa beta (NF-ĸB), mechanistic target of rapamycin (mTOR) and sirtuins (SIRTs)), all the pathways except SIRT were altered in a manner consistent with increased lifespan...
July 31, 2017: Aging
https://www.readbyqxmd.com/read/28767699/molecular-evolutionary-patterns-of-nad-sirtuin-aging-signaling-pathway-across-taxa
#11
Uma Gaur, Jianbo Tu, Diyan Li, Yue Gao, Ting Lian, Boyuan Sun, Deying Yang, Xiaolan Fan, Mingyao Yang
A deeper understanding of the conserved molecular mechanisms in different taxa have been made possible only because of the evolutionary conservation of crucial signaling pathways. In the present study, we explored the molecular evolutionary pattern of selection signatures in 51 species for 10 genes which are important components of NAD+/Sirtuin pathway and have already been directly linked to lifespan extension in worms and mice. Selection pressure analysis using PAML program revealed that MRPS5 and PPARGC1A were under significant constraints because of their functional significance...
2017: PloS One
https://www.readbyqxmd.com/read/28765962/sirt1-activation-inhibits-hyperglycemia-induced-apoptosis-by-reducing-oxidative-stress-and-mitochondrial-dysfunction-in-human-endothelial-cells
#12
Shengqiang Wang, Jian Wang, Airong Zhao, Jigang Li
Sustained hyperglycemic stimulation of vascular cells is involved in the pathogenesis of diabetes mellitus‑induced cardiovascular complications. Silent information regulator T1 (SIRT1), a mammalian sirtuin, has been previously recognized to protect endothelial cells against hyperglycemia‑induced oxidative stress. In the present study, human umbilical vein endothelial cells (HUV‑EC‑C) were treated with D‑glucose, and the levels of oxidative stress, mitochondrial dysfunction, the rate of apoptosis and SIRT1 activity were measured...
September 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28765952/mtor-signaling-promotes-foam-cell-formation-and-inhibits-foam-cell-egress-through-suppressing-the-sirt1-signaling-pathway
#13
Haixiang Zheng, Yucai Fu, Yusheng Huang, Xinde Zheng, Wei Yu, Wei Wang
Atherosclerosis (AS) is a chronic immuno‑inflammatory disease accompanied by dyslipidemia. The authors previously demonstrated that sirtuin 1 (SIRT1) may prevent atherogenesis through influencing the liver X receptor/C‑C chemokine receptor type 7/nuclear factor‑κB (LXR‑CCR7/NF‑κB) signaling pathway. Previous studies have suggested a role for mammalian target of rapamycin (mTOR) signaling in the pathogenesis of cardiovascular diseases. The present study investigated the potential association between mTOR signaling and SIRT1‑LXR‑CCR7/NF‑κB signaling (SIRT1 signaling) in AS pathogenesis...
September 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28762752/oxidative-stress-in-mesenchymal-stem-cell-senescence-regulation-by-coding-and-non-coding-rnas
#14
Rosa Vono, Eva Jover Garcia, Gaia Spinetti, Paolo Madeddu
SIGNIFICANCE: Mesenchymal stem cells (MSCs), adult stem cells with the potential of differentiation into mesodermal lineages, play an important role in tissue homeostasis and regeneration. In different organs, a subpopulation of MSCs is located near to the vasculature and possibly represents the original source of lineage-committed mesenchymal progenitors. Recent Advances. The plasticity and immune characteristics of MSCs render them a preferential tool for regenerative cell therapy. CRITICAL ISSUES: The culture expansion needed before MSC transplantation is associated with cellular senescence...
August 1, 2017: Antioxidants & Redox Signaling
https://www.readbyqxmd.com/read/28760703/berberine-induced-cardioprotection-and-sirt3-modulation-in-doxorubicin-treated-h9c2-cardiomyoblasts
#15
Ana R Coelho, Tatiana R Martins, Renata Couto, Cláudia Deus, Cláudia V Pereira, Rui F Simões, Albert A Rizvanov, Filomena Silva, Teresa Cunha-Oliveira, Paulo J Oliveira, Teresa L Serafim
Doxorubicin (DOX) is one of the most widely used anti-neoplastic agents. However, treatment with DOX is associated with cumulative cardiotoxicity inducing progressive cardiomyocyte death. Sirtuin 3 (Sirt3), a mitochondrial deacetylase, regulates the activity of proteins involved in apoptosis, autophagy and metabolism. Our hypothesis is that pharmacological modulation by berberine (BER) pre-conditioning of Sirt3 protein levels decreases DOX-induced cardiotoxicity. Our results showed that DOX induces cell death in all experimental groups...
July 28, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28757161/adventitial-sca-1-progenitor-cell-gene-sequencing-reveals-the-mechanisms-of-cell-migration-in-response-to-hyperlipidemia
#16
Ioannis Kokkinopoulos, Mei Mei Wong, Claire M F Potter, Yao Xie, Baoqi Yu, Derek T Warren, Witold N Nowak, Alexandra Le Bras, Zhichao Ni, Chao Zhou, Xiongzhong Ruan, Eirini Karamariti, Yanhua Hu, Li Zhang, Qingbo Xu
Adventitial progenitor cells, including SCA-1(+) and mesenchymal stem cells, are believed to be important in vascular remodeling. It has been shown that SCA-1(+) progenitor cells are involved in neointimal hyperplasia of vein grafts, but little is known concerning their involvement in hyperlipidemia-induced atherosclerosis. We employed single-cell sequencing technology on primary adventitial mouse SCA-1(+) cells from wild-type and atherosclerotic-prone (ApoE-deficient) mice and found that a group of genes controlling cell migration and matrix protein degradation was highly altered...
August 8, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/28756638/structure-based-discovery-of-new-selective-small-molecule-sirtuin-5-inhibitors
#17
Sha Liu, Sen Ji, Zhu-Jun Yu, Hua-Li Wang, Xu Cheng, Wei-Jian Li, Li Jing, Yamei Yu, Qiang Chen, Ling-Ling Yang, Guo-Bo Li, Yong Wu
Human sirtuin 5 (SIRT5) is a protein deacylase regulating metabolic pathways and stress responses, and is implicated in metabolism-related diseases. Small molecule inhibitors for SIRT5 are sought as chemical tools and potential therapeutics. Herein we proposed a customized virtual screening approach targeting catalytically important and unique residues Tyr102 and Arg105 of SIRT5. Of the 20 tested virtual screening hits, 6 compounds displayed marked inhibitory activities against SIRT5. For the hit compound 19, a series of new synthesized (E)-2-cyano-N-phenyl-3-(5-phenylfuran-2-yl)acrylamide derivatives/analogues were carried out structure-activity relationship analyses, resulting in new more potent inhibitors, among which 37 displayed the most potent inhibition to SIRT5 with an IC50 value of 5...
July 30, 2017: Chemical Biology & Drug Design
https://www.readbyqxmd.com/read/28756024/design-synthesis-and-anticancer-activity-of-n-1-4-dibenzo-b-f-1-4-thiazepin-11-yl-piperazin-1-yl-1-oxo-3-phenylpropan-2-yl-derivatives
#18
Mura Reddy Gudisela, N Srinivasu, Chaitanya Mulakayala, Praveen Bommu, M V Basaveswara Rao, Naveen Mulakayala
Novel N-(1-(4-(dibenzo[b,f][1,4]thiazepin-11-yl)piperazin-1-yl)-1-oxo-3-phenylpropan-2-yl derivatives were designed, synthesized and their chemical structures were confirmed by (1)H NMR, (13)C NMR and Mass spectra. The anticancer activities of the newly synthesized compounds were evaluated in vitro against three human cancer cell lines including HCT-116, Hun7 and SW620 by MTT assay. The screening results showed that five compounds (16b, 16d, 16i, 16p and 16q) exhibited potent cytotoxic activities with IC50 values between 20 and 40μM...
July 11, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28755171/sirt1-induces-resistance-to-apoptosis-in-human-granulosa-cells-by-activating-the-erk-pathway-and-inhibiting-nf-%C3%AE%C2%BAb-signaling-with-anti-inflammatory-functions
#19
Ying Han, Haining Luo, Hui Wang, Jun Cai, Yunshan Zhang
SIRT1, a member of the sirtuin family, has recently emerged as a vital molecule in controlling ovarian function. The aims of the present study were to investigate SIRT1 expression and analyze SIRT1-mediated apoptosis in human granulosa cells (GCs). Human ovarian tissues were subjected to immunohistochemistry for localization of SIRT1 expression. SIRT1 knockdown in a human ovarian GC tumor line (COV434) was achieved by small interfering RNA, and the relationship between apoptosis and SIRT1 was assessed by quantitative reverse transcription polymerase chain reaction and western blotting...
July 28, 2017: Apoptosis: An International Journal on Programmed Cell Death
https://www.readbyqxmd.com/read/28754906/kras-activation-and-over-expression-of-sirt1-bcl6-contributes-to-the-pathogenesis-of-endometriosis-and-progesterone-resistance
#20
Jung-Yoon Yoo, Tae Hoon Kim, Asgerally T Fazleabas, Wilder A Palomino, Soo Hyun Ahn, Chandrakant Tayade, David P Schammel, Steven L Young, Jae-Wook Jeong, Bruce A Lessey
Endometriosis is an inflammatory condition that is associated with progesterone resistance and cell proliferation, resulting in pain, infertility and pregnancy loss. We previously demonstrated phosphorylation of STAT3 in eutopic endometrium of infertile women with this disorder leading to over-expression of the oncogene BCL6 and stabilization of hypoxia-induced factor 1 alpha (HIF-1α). Here we report coordinated activation of KRAS and over-expression of Sirtuin 1 (SIRT1), a histone deacetylase and gene silencer, in the eutopic endometrium from women with endometriosis throughout the menstrual cycle...
July 28, 2017: Scientific Reports
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