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https://www.readbyqxmd.com/read/29721988/role-of-sirtuins-in-retinal-function-under-basal-conditions
#1
Jonathan B Lin, Shunsuke Kubota, Raul Mostoslavsky, Rajendra S Apte
Sirtuins are NAD+ -dependent enzymes that govern cellular homeostasis by regulating the acylation status of their diverse target proteins. We recently demonstrated that both rod and cone photoreceptors rely on NAMPT-mediated NAD+ biosynthesis to meet their energetic requirements. Moreover, we found that this NAD+ -dependent retinal homeostasis relies, in part, on maintenance of optimal activity of the mitochondrial sirtuins and of SIRT3 in particular. Nonetheless, it is unknown whether other sirtuin family members also play important roles in retinal homeostasis...
2018: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/29719779/a-pilot-study-of-the-modulation-of-sirtuins-on-arylamine-n-acetyltransferase-1-and-2-enzymatic-activity
#2
Eneida Turiján-Espinoza, Rául Alejandro Salazar-González, Edith Elena Uresti-Rivera, Gloria Estela Hernández-Hernández, Montserrat Ortega-Juárez, Rosa Milán, Diana Portales-Pérez
Arylamine N -acetyltransferase (NAT; E.C. 2.3.1.5) enzymes are responsible for the biotransformation of several arylamine and hydrazine drugs by acetylation. In this process, the acetyl group transferred to the acceptor substrate produces NAT deacetylation and, in consequence, it is susceptible of degradation. Sirtuins are protein deacetylases, dependent on nicotine adenine dinucleotide, which perform post-translational modifications on cytosolic proteins. To explore possible sirtuin participation in the enzymatic activity of arylamine NATs, the expression levels of NAT1, NAT2, SIRT1 and SIRT6 in peripheral blood mononuclear cells (PBMC) from healthy subjects were examined by flow cytometry and Western blot...
March 2018: Acta Pharmaceutica Sinica. B
https://www.readbyqxmd.com/read/29717979/boosting-atm-activity-alleviates-ageing-and-extends-lifespan-in-a-mouse-model-of-progeria
#3
Minxian Qian, Zuojun Liu, Linyuan Peng, Xiaolong Tang, Fanbiao Meng, Ying Ao, Mingyan Zhou, Ming Wang, Xinyue Cao, Baoming Qin, Zimei Wang, Zhongjun Zhou, Guangming Wang, Zhengliang Gao, Xu Jun, Baohua Liu
DNA damage accumulates with age (Lombard et al., 2005). However, whether and how robust DNA repair machinery promotes longevity is elusive. Here, we demonstrate that ATM-centered DNA damage response (DDR) progressively declines with senescence and age, while low dose of chloroquine (CQ) activates ATM, promotes DNA damage clearance, rescues age-related metabolic shift, and prolongs replicative lifespan. Molecularly, ATM phosphorylates SIRT6 deacetylase and thus prevents MDM2-mediated ubiquitination and proteasomal degradation...
May 2, 2018: ELife
https://www.readbyqxmd.com/read/29712732/sirtuins-in-renal-health-and-disease
#4
REVIEW
Marina Morigi, Luca Perico, Ariela Benigni
Sirtuins belong to an evolutionarily conserved family of NAD+ -dependent deacetylases that share multiple cellular functions related to proliferation, DNA repair, mitochondrial energy homeostasis, and antioxidant activity. Mammalians express seven sirtuins (SIRT1-7) that are localized in different subcellular compartments. Changes in sirtuin expression are critical in several diseases, including metabolic syndrome, diabetes, cancer, and aging. In the kidney, the most widely studied sirtuin is SIRT1, which exerts cytoprotective effects by inhibiting cell apoptosis, inflammation, and fibrosis together with SIRT3, a crucial metabolic sensor that regulates ATP generation and mitochondrial adaptive response to stress...
April 30, 2018: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/29698567/ubiquitin-specific-peptidase-10-usp10-inhibits-hepatic-steatosis-insulin-resistance-and-inflammation-via-sirt6
#5
Pengcheng Luo, Cong Qin, Lihua Zhu, Chun Fang, Yan Zhang, Hai Zhang, Fei Pei, Song Tian, Xue-Yong Zhu, Gong Jun, Qing Mao, Chengcheng Xiao, Yang Su, Haizhou Zheng, Tao Xu, Jingxiao Lu, Jie Zhang
BACKGROUND AND AIMS: Nonalcoholic fatty liver disease (NAFLD) is characterized by hepatic steatosis, insulin resistance and inflammation, and the pathogenic mechanism of NAFLD is poorly understood. Ubiquitin-specific peptidase 10 (USP10), a member of the ubiquitin-specific protease (USP) family, is involved in environmental stress responses, tumor growth, inflammation and cellular metabolism. However, the role of USP10 in hepatic steatosis, insulin resistance and inflammation remains largely unexplored...
April 26, 2018: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/29686974/sirt6-acts-as-a-negative-regulator-in-dengue-virus-induced-inflammatory-response-by-targeting-the-dna-binding-domain-of-nf-%C3%AE%C2%BAb-p65
#6
Pengcheng Li, Yufei Jin, Fei Qi, Fangyi Wu, Susu Luo, Yuanjiu Cheng, Ruth R Montgomery, Feng Qian
Dengue virus (DENV) is a mosquito-borne single-stranded RNA virus causing human disease with variable severity. The production of massive inflammatory cytokines in dengue patients has been associated with dengue disease severity. However, the regulation of these inflammatory responses remains unclear. In this study, we report that SIRT6 is a negative regulator of innate immune responses during DENV infection. Silencing of Sirt6 enhances DENV-induced proinflammatory cytokine and chemokine production. Overexpression of SIRT6 inhibits RIG-I-like receptor (RLR) and Toll-like receptor 3 (TLR3) mediated NF-κB activation...
2018: Frontiers in Cellular and Infection Microbiology
https://www.readbyqxmd.com/read/29686722/energy-restriction-exercise-and-atorvastatin-treatment-improve-endothelial-dysfunction-and-inhibit-mirna-155-in-the-erectile-tissue-of-the-aged-rat
#7
B Rocha, A R Rodrigues, I Tomada, M J Martins, J T Guimarães, A M Gouveia, H Almeida, D Neves
Background: Endothelial dysfunction underlies cardiovascular disease that frequently affects aged individuals. Characterized by local decrease in nitric oxide, it results from down-regulation of endothelial nitric oxide synthase (eNOS) expression/activity. Aiming to elucidate the molecular mechanisms involved in age-related endothelial dysfunction and to unveil potential therapeutic targets, we tested how diet pattern, exercise and atorvastatin modulate the expression of eNOS, inducible NOS (iNOS), endothelin-1, sirtuins (SIRT) and microRNA-155 in the erectile tissue of high-fat fed aged rats...
2018: Nutrition & Metabolism
https://www.readbyqxmd.com/read/29659670/histone-deacetylase-sirt6-inhibits-glioma-cell-growth-through-down-regulating-notch3-expression
#8
Xin Chen, Deheng Li, Yang Gao, Yiqun Cao, Bin Hao
Gliomas are the most common brain tumors of the central nervous system. In this study, we investigated the molecular mechanisms and biological function of SIRT6 in human gliomas. The expression levels of SIRT6 in glioma tissues and cells were analyzed by qRT-PCR and western blot analysis. CCK8 and clonogenicity assays were performed to detect the cell proliferation. Furthermore, the migration and invasion of glioma cells were examined by transwell assays. It was found that the expression of SIRT6 was significantly lower in human glioma tissues or cell lines compared with the normal brain tissue or NHA...
April 1, 2018: Acta Biochimica et Biophysica Sinica
https://www.readbyqxmd.com/read/29657112/high-expression-of-cpt1b-in-skeletal-muscle-in-metabolically-healthy-older-subjects
#9
C Bétry, E Meugnier, M Pflieger, G Grenet, S Hercberg, P Galan, E Kesse-Guyot, H Vidal, M Laville
AIM: Ageing is often associated with metabolic abnormalities such as insulin resistance, although some people remain metabolically healthy throughout their lives. The aim of this study was to gain more insight into metabolic health with increasing age. METHODS: Two groups of robust and of frail subjects, respectively, were identified based on a composite ageing indicator and recruited from the French SU.VI.MAX 2 cohort of older disease-free subjects. In all, 14 men and 12 women, aged 67±4 years, with similar anthropometric and metabolic characteristics at baseline (BMI: 24...
February 12, 2018: Diabetes & Metabolism
https://www.readbyqxmd.com/read/29599436/sirt6-facilitates-directional-telomere-movement-upon-oxidative-damage
#10
Ying Gao, Jun Tan, Jingyi Jin, Hongqiang Ma, Xiukai Chen, Brittany Leger, Jianquan Xu, Stephen T Spagnol, Kris Noel Dahl, Arthur S Levine, Yang Liu, Li Lan
Oxidative damage to telomeres leads to telomere attrition and genomic instability, resulting in poor cell viability. Telomere dynamics contribute to the maintenance of telomere integrity; however, whether oxidative damage induces telomere movement and how telomere mobility is regulated remain poorly understood. Here, we show that oxidative damage at telomeres triggers directional telomere movement. The presence of the human Sir2 homolog, Sirtuin 6 (SIRT6) is required for oxidative damage-induced telomeric movement...
March 29, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29563873/sirt6-depletion-sensitizes-human-hepatoma-cells-to-chemotherapeutics-by-downregulating-mdr1-expression
#11
Yang Q Xia, Ren J Hua, Chen Juan, Zhou H Zhong, Cheng S Tao, Ren Fang, He Lin, Gong Rui, Chen Yong
Multidrug resistance (MDR) due to overexpression of MDR1 is a major obstacle that hinders the treatment of hepatocellular carcinoma (HCC). In this study, we explored the function and underlying molecular mechanism of SIRT6 in MDR of HCC. Chemotherapeutic agents (doxorubicin, cisplatin, and sorafenib) treatment increased SIRT6 mRNA and protein level in two HCC cell lines in a dose-dependent manner. SIRT6 depletion resulted in decreased cell viability and increased apoptosis in HCC cells treated with chemotherapeutic agents...
2018: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/29557214/current-understanding-and-future-perspectives-of-the-roles-of-sirtuins-in-the-reprogramming-and-differentiation-of-pluripotent-stem-cells
#12
Yi-Chao Hsu, Yu-Ting Wu, Chia-Ling Tsai, Yau-Huei Wei
In mammalian cells, there are seven members of the sirtuin protein family (SIRT1-7). SIRT1, SIRT6, and SIRT7 catalyze posttranslational modification of proteins in the nucleus, SIRT3, SIRT4, and SIRT5 are in the mitochondria and SIRT2 is in the cytosol. SIRT1 can deacetylate the transcription factor SOX2 and regulate induced pluripotent stem cells (iPSCs) reprogramming through the miR-34a-SIRT1-p53 axis. SIRT2 can regulate the function of pluripotent stem cells through GSK3β. SIRT3 can positively regulate PPAR gamma coactivator 1-alpha (PGC-1α) expression during the differentiation of stem cells...
March 2018: Experimental Biology and Medicine
https://www.readbyqxmd.com/read/29556059/molecular-insights-into-the-interaction-of-rons-and-thieno-3-2-c-pyran-analogs-with-sirt6-cox-2-a-molecular-dynamics-study
#13
Dharmendra K Yadav, Surendra Kumar, Saloni, Sanjeev Misra, Lalit Yadav, Mahesh Teli, Praveen Sharma, Sandeep Chaudhary, Naresh Kumar, Eun Ha Choi, Hyung Sik Kim, Mi-Hyun Kim
SIRT6 and COX-2 are oncogenes target that promote the expression of proinflammatory and pro-survival proteins through a signaling pathway, which leads to increased survival and proliferation of tumor cells. However, COX-2 also suppresses skin tumorigenesis and their relationship with SIRT6, making it an interesting target for the discovery of drugs with anti-inflammatory and anti-cancer properties. Herein, we studied the interaction of thieno[3,2-c]pyran analogs and RONS species with SIRT6 and COX-2 through the use of molecular docking and molecular dynamic simulations...
March 19, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29555651/an-inactivating-mutation-in-the-histone-deacetylase-sirt6-causes-human-perinatal-lethality
#14
Christina M Ferrer, Marielle Alders, Alex V Postma, Seonmi Park, Mark A Klein, Murat Cetinbas, Eva Pajkrt, Astrid Glas, Silvana van Koningsbruggen, Vincent M Christoffels, Marcel M A M Mannens, Lia Knegt, Jean-Pierre Etchegaray, Ruslan I Sadreyev, John M Denu, Gustavo Mostoslavsky, Merel C van Maarle, Raul Mostoslavsky
It has been well established that histone and DNA modifications are critical to maintaining the equilibrium between pluripotency and differentiation during early embryogenesis. Mutations in key regulators of DNA methylation have shown that the balance between gene regulation and function is critical during neural development in early years of life. However, there have been no identified cases linking epigenetic regulators to aberrant human development and fetal demise. Here, we demonstrate that a homozygous inactivating mutation in the histone deacetylase SIRT6 results in severe congenital anomalies and perinatal lethality in four affected fetuses...
March 1, 2018: Genes & Development
https://www.readbyqxmd.com/read/29552180/sirt6-inhibits-colorectal-cancer-stem-cell-proliferation-by-targeting-cdc25a
#15
Wenguang Liu, Manwu Wu, Hechun Du, Xiaoliang Shi, Tao Zhang, Jie Li
Silent information regulator 6 (SIRT6) is broadly considered as a tumor suppressor due to its function in the suppression of oncogene expression. However, the role of SIRT6 in colorectal cancer stem cells (CSCs) remains uncharacterized. In the present study, it was demonstrated that SIRT6 expression was reduced in colorectal CSCs. Overexpression of SIRT6 in colorectal CSCs did not induce cell apoptosis. However, SIRT6 significantly inhibited cell proliferation, colony formation and induced G0/G1 phase arrest in colorectal CSCs...
April 2018: Oncology Letters
https://www.readbyqxmd.com/read/29535637/the-role-of-sirt6-in-obesity-and-diabetes
#16
REVIEW
Jiangying Kuang, Lei Chen, Qin Tang, Jinhang Zhang, Yanping Li, Jinhan He
Sirt6 is one of the sirtuin family members, a kind of NAD+-dependent histone deacetylase and ADP-ribose transferase enzyme. It has an important role in physiological and pathological processes, regulating aging, cancer, obesity, insulin resistance, inflammation, and energy metabolism. Recent studies have suggested that reduced Sirt6 action is related to obesity and diabetes. Aging and overnutrition, two major risk factors for obesity and diabetes, lead to decreased Sirt6 level and function, which results in abnormal glucose and lipid metabolism...
2018: Frontiers in Physiology
https://www.readbyqxmd.com/read/29535552/coordination-of-foxa2-and-sirt6-suppresses-the-hepatocellular-carcinoma-progression-through-zeb2-inhibition
#17
Jinghua Liu, Zhen Yu, Yuanyuan Xiao, Qiong Meng, Yeying Wang, Wei Chang
Background: The Forkhead transcription family member FOXA2 plays a fundamental role in hepatocellular carcinoma (HCC) progression, but the precise interaction factor and molecular regulation of FOXA2 are not fully understood. Objective: In this study, we found that FOXA2 could interact with sirtuin 6 (SIRT6) directly in vivo and in vitro. We explored that the expressions of FOXA2 and SIRT6 were significantly downregulated in human HCC and HCC cell lines. Methods: Functionally, cell counting kit-8 assay and Transwell® assay were performed; we demonstrated that the knockdown of FOXA2 and SIRT6 promoted HepG2 cells and Huh7 cells proliferation and invasion in vitro...
2018: Cancer Management and Research
https://www.readbyqxmd.com/read/29515203/natural-polyphenols-as-sirtuin-6-modulators
#18
Minna Rahnasto-Rilla, Jonna Tyni, Marjo Huovinen, Elina Jarho, Tomasz Kulikowicz, Sarangan Ravichandran, Vilhelm A Bohr, Luigi Ferrucci, Maija Lahtela-Kakkonen, Ruin Moaddel
Flavonoids are polyphenolic secondary metabolites synthesized by plants and fungus with various pharmacological effects. Due to their plethora of biological activities, they have been studied extensively in drug development. They have been shown to modulate the activity of a NAD+ -dependent histone deacetylase, SIRT6. Because SIRT6 has been implicated in longevity, metabolism, DNA-repair, and inflammatory response reduction, it is an interesting target in inflammatory and metabolic diseases as well as in cancer...
March 7, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29512733/autophagy-inhibition-enhanced-5%C3%A2-fu%C3%A2-induced-cell-death-in-human-gastric-carcinoma-bgc%C3%A2-823-cells
#19
Xing-Xing He, Chen-Kai Huang, Bu-Shan Xie
The exact molecular mechanism of 5-fluorouracil (5-FU) in human gastric cancer cells remains to be elucidated. Cultured BGC‑823 human gastric carcinoma and AGS cell lines were treated with 5‑FU. Autophagosome formation was investigated through multiple approaches, including the quantification of green fluorescent protein‑microtubule‑associated protein 1A/1B‑light chain 3 (LC3) puncta, LC3 conversion and electron microscopy observations. Additionally, autophagy was inhibited using 3‑methyladenine (3‑MA) and beclin‑1 ablation, to determine its role in 5‑FU‑mediated cell death...
May 2018: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29512698/downregulation-of-sirt6-by-mir-34c-5p-is-associated-with-poor-prognosis-and-promotes-colon-cancer-proliferation-through-inhibiting-apoptosis-via-the-jak2-stat3-signaling-pathway
#20
Ning Li, Dong Mao, Yansha Cao, Hua Li, Fu Ren, Keyan Li
Sirtuin 6 (SIRT6) is a member of the nicotinamide adenine dinucleotide positivity-dependent class III deacetylase sirtuin family. The present study aimed to explore the expression and function of SIRT6 in colon cancer. Furthermore, the partial mechanism underlying the dysregulation of SIRT6 was investigated. The results of immunohistochemistry demonstrated that SIRT6 was markedly downregulated in colon cancer tissues, and patients with high SIRT6 expression had a better prognosis than those who did not. The proliferation and apoptotic assays demonstrated that SIRT6 was able to suppress colon cancer cell proliferation and induce apoptosis via the Janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) signaling pathway...
March 5, 2018: International Journal of Oncology
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