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Isabella P P Grande, Paulo V G H Amorim, Ane Caroline Thé B Freire, Raquel S Jallad, Nina R Musolino, Valter A Cescato, Gilberto O da Silva, Marcello D Bronstein, Ericka B Trarbach
Sirtuins 1-7 (SIRT) are a highly conserved family of histone deacetylases involved in the regulation of longevity that have a considerable impact in transcription, DNA repair regulation, telomeric stability, cell senescence and apoptosis. In the present study, SIRT1-7 mRNA levels were evaluated in 37 somatotropinomas and 31 nonfunctioning pituitary adenomas (NFPAs) using qPCR and relation to tumor size, invasiveness and Ki-67 proliferative index was made. Overexpression of SIRT1 was observed in 86.5% of somatotropinomas versus 41...
March 21, 2018: Pituitary
José A Del Campo, Rocío Gallego-Durán, Paloma Gallego, Lourdes Grande
Genetics and epigenetics play a key role in the development of several diseases, including nonalcoholic fatty liver disease (NAFLD). Family studies demonstrate that first degree relatives of patients with NAFLD are at a much higher risk of the disease than the general population. The development of the Genome Wide Association Study (GWAS) technology has allowed the identification of numerous genetic polymorphisms involved in the evolution of diseases (e.g., PNPLA3 , MBOAT7 ). On the other hand, epigenetic changes interact with inherited risk factors to determine an individual's susceptibility to NAFLD...
March 19, 2018: International Journal of Molecular Sciences
Yun Wang, Qing-Jiang Pang, Jiang-Tao Liu, Hai-Hao Wu, Dong-Ying Tao
MicroRNAs play a crucial role in the progression of spinal cord ischemia/reperfusion injury (SCII). The role of miR-448 and SIRT1 in SCII was investigated in this study, to provide further insights into prevention and improvement of this disorder. In this study, expressions of miR-448 and SIRT1 protein were determined by qRT-PCR and western blot, respectively. Flow cytometry was used to analyze cell apoptosis. The endogenous expression of genes was modulated by recombinant plasmids and cell transfection. Dual-luciferase reporter assay was performed to determine the interaction between miR-448 and SIRT1...
March 15, 2018: Brazilian Journal of Medical and Biological Research, Revista Brasileira de Pesquisas Médicas e Biológicas
Tanusree Sen, Pampa Saha, Nilkantha Sen
Acetylation of the microtubule-associated protein tau promotes its polymerization into neurofibrillary tangles that are implicated in the pathology of Alzheimer's disease (AD). The gaseous neurotransmitter nitric oxide (NO) regulates cell signaling through the nitrosylation of proteins. We found that NO production and tau acetylation at Lys280 occurred in the brain tissue in mice and in cultured mouse cortical neurons in response to exposure to amyloid-β1-42 (Aβ1-42 ), a peptide that is also implicated in AD...
March 20, 2018: Science Signaling
Kenneth Maiese
BACKGROUND: With the global increase in life span expectancy, neurodegenerative disorders continue to affect an ever increasing number of individuals throughout the world. New treatment strategies for neurodegenerative diseases are desperately required given the lack of current treatment modalities. METHODS: Here we examine novel strategies for neurodegenerative disorders that include circadian clock genes, non-coding ribonucleic acids (RNAs), and the mammalian forkhead transcription factors of the O class (FoxOs)...
March 19, 2018: Current Neurovascular Research
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
Qi-Bing Wu, Xin Sheng, Ning Zhang, Ming-Wei Yang, Fan Wang
Colorectal cancer (CRC) is among the main tumor-related causes of death worldwide. The fact that the majority of the patients develop resistance to chemoradiotherapy (CRT) is a major obstacle for the treatment of CRC. In order to develop more effective treatment strategies, it is crucial to elucidate the mechanisms underlying the development of resistance to CRT. Several studies have recently indicated the regulatory effects of microRNAs (miRNAs) in response to antitumor agents. For example, miR-34a attenuates the chemoresistance of colon cancer to 5-FU by inhibiting E2F3 and SIRT1...
April 2018: Molecular and Clinical Oncology
Sifan Chen, Zhongliang Zhao, Liangru Ke, Zilun Li, Wenxue Li, Zili Zhang, Ying Zhou, Xiang Feng, Wei Zhu
Insulin resistance serves as "common soil" for promoting the development of metabolic diseases; however, the precise pathological factors leading to insulin resistance are not well clarified. Resveratrol (Res) is a natural polyphenolic compound with anti-inflammatory and antioxidative effects. However, effects and mechanisms of Res on glucose metabolism in adipocytes remain largely unknown. In this study, we show Res treatment significantly increases glucose uptake in insulin-resistant 3T3-L1 adipocytes in vitro...
February 13, 2018: Journal of Nutritional Biochemistry
Fushen Yang
PURPOSE: To investigate the expression of sirtuin type 1 (Sirt1) and adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK) in non-small cell lung cancer (NSCLC), and to explore the mechanism of their functions in NSCLC. METHODS: Cancer tissues (NSCLC group) and the adjacent normal healthy tissues (control group) of 50 patients with NSCLC were selected, and H&E staining was performed to identify the histopathological differences. Reverse transcription polymerase chain reaction (RT-PCR), immunofluorescence staining and Western blot were performed to detect the expression of Sirt1 and AMPK in tissues of NSCLC group and control group...
January 2018: Journal of B.U.ON.: Official Journal of the Balkan Union of Oncology
Hui Liu, Xin-Hua Cheng
Oxaliplatin is a commonly used chemotherapeutic drug for the treatment of advanced colorectal cancer. However, acquired drug resistance against oxaliplatin remains a major obstacle for efficient use of it, and mechanisms underlying oxaliplatin resistance are still required to be explored. In the present study, we exposed colorectal cancer cell line SW480 to oxaliplatin for a long time to obtain oxaliplatin-resistant colorectal cancer cell model (OR-SW480). We found that intracellular expression of miR-29b was decreased when the SW480 cells became oxaliplatin-resistant...
February 23, 2018: Oncotarget
Shalem Modi, Nagendra Yaluri, Tarja Kokkola
Obesity is characterized by excess fat accumulation in white adipose tissue, which triggers chronic low-grade inflammation through secretion of pro-inflammatory factors by the enlarged adipocytes and infiltrated macrophages. This affects glucose and lipid metabolism in adipose tissue, inducing type 2 diabetes. NAD+ -dependent deacetylase SIRT1 is known to inhibit adipogenesis through the regulation of the key adipogenic transcription factors, PPARγ and C/EBPα. SIRT1 activators such as resveratrol inhibit adipogenesis and exert anti-inflammatory responses in the adipose tissue...
March 14, 2018: Biochemical and Biophysical Research Communications
Hilal Ahmad Parray, Jameel Lone, Jong Pil Park, Jang Won Choi, Jong Won Yun
OBJECTIVE: The aim of this study was to explore the browning and antioxidative effects of magnolol in 3T3-L1 adipocytes, as recruitment of beige-like adipocytes (browning) by natural compounds is being considered as a promising strategy to fight against obesity. METHODS: Magnolol-induced browning effect was evaluated by determining the expression levels of specific marker genes and proteins using real-time polymerase chain reaction and immunoblotting, respectively...
February 5, 2018: Nutrition
Xiangying Guan, Alok Upadhyay, Sudipto Munshi, Raj Chakrabarti
Across all families of enzymes, only a dozen or so distinct classes of non-natural small molecule activators have been characterized, with only four known modes of activation among them. All of these modes of activation rely on naturally evolved binding sites that trigger global conformational changes. Among the enzymes that are of greatest interest for small molecule activation are the seven sirtuin enzymes, nicotinamide adenine dinucleotide (NAD+)-dependent protein deacylases that play a central role in the regulation of healthspan and lifespan in organisms ranging from yeast to mammals...
2018: PloS One
Lucyna Kaszubowska, Jerzy Foerster, Jan Jacek Kaczor, Daria Schetz, Tomasz Jerzy Ślebioda, Zbigniew Kmieć
Background: Natural killer cells (NK cells) are cytotoxic lymphocytes of innate immunity that reveal some immunoregulatory properties, however, their role in the process of ageing is not completely understood. The study aimed to analyze the expression of proteins involved in cellular stress response: sirtuin 1 (SIRT1), heat shock protein 70 (HSP70) and manganese superoxide dismutase (SOD2) in human NK cells with reference to the process of ageing. Non-stimulated and stimulated with IL-2, LPS or PMA with ionomycin cells originated from peripheral blood samples of: seniors aged over 85 ('the oldest'; n  = 25; 88...
2018: Immunity & Ageing: I & A
Sang-Won Min, Peter Dongmin Sohn, Yaqiao Li, Nino Devidze, Jeffrey R Johnson, Nevan J Krogan, Eliezer Masliah, Sue-Ann Mok, Jason E Gestwicki, Li Gan
Hyperacetylation of tau has been implicated in neurodegeneration and cognitive decline in tauopathy brains. The NAD-dependent class III protein deacetylase SIRT1 is one of major enzymes involved in removal of acetyl groups from tau in vitro However, whether SIRT1 regulates acetylation of pathogenic tau and ameliorates tau-mediated pathogenesis remains unclear. Here, we report deacetylating activity of SIRT1 for acetylated Lys174 (K174) of tau in tauP301S transgenic mice with a brain-specific SIRT1 deletion...
March 14, 2018: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
Sara Bianchi, Luca Giovannini
The mTOR pathway plays a crucial role in many human diseases, mostly associated with an over hyperactivity of the mTOR signaling, which makes its inhibitors potentially effective therapeutics. Thus, it is important to consider not only the mTOR pathway, but also all those factors that play a key role in its regulation, such as SIRT1 and AMPK. We previously demonstrated the role of some nutraceutical SIRT1 modulators in AMPK and mTOR pathway, showing the presence of a synergistic effect. Now we take further our research by evaluating the effect of berberine, quercetin, tyrosol, and ferulic acid on the mTOR/S6K1/4E-BP1 signaling, along with the existence of any synergistic effect between the following associations: berberine + tyrosol, tyrosol + ferulic acid, ferulic acid + quercetin...
March 14, 2018: Nutrition and Cancer
Andrew Leber, Raquel Hontecillas, Nuria Tubau-Juni, Victoria Zoccoli-Rodriguez, Vida Abedi, Josep Bassaganya-Riera
Interactions among the gut microbiome, dysregulated immune responses, and genetic factors contribute to the pathogenesis of inflammatory bowel disease (IBD). Nlrx1 -/- mice have exacerbated disease severity, colonic lesions, and increased inflammatory markers. Global transcriptomic analyses demonstrate enhanced mucosal antimicrobial defense response, chemokine and cytokine expression, and epithelial cell metabolism in colitic Nlrx1 -/- mice compared to wild-type (WT) mice. Cell-specificity studies using cre-lox mice demonstrate that the loss of NLRX1 in intestinal epithelial cells (IEC) recapitulate the increased sensitivity to DSS colitis observed in whole body Nlrx1 -/- mice...
2018: Frontiers in Immunology
Xuejiao Li, Zhongxiu Jiang, Xiangmin Li, Xiaoye Zhang
Osteopontin (OPN) is a promoter for tumor progression. It has been reported to promote non-small cell lung cancer (NSCLC) progression via the activation of nuclear factor-κB (NF-κB) signaling. As the increased acetylation of NF-κB p65 is linked to NF-κB activation, the regulation of NF-κB p65 acetylation could be a potential treatment target for OPN-induced NSCLC progression. Sirtuin 1 (SIRT1) is a deacetylase, and the role of SIRT1 in tumor progression is still controversial. The effect and mechanism of SIRT1 on OPN-induced tumor progression remains unknown...
2018: OncoTargets and Therapy
Shuyi Wang, Cong Wang, Subat Turdi, Kacy L Richmond, Yingmei Zhang, Jun Ren
BACKGROUND AND AIMS: Uncorrected obesity contributes to cardiac remodeling and contractile dysfunction although the underlying mechanism remains poorly understood. Mitochondrial aldehyde dehydrogenase (ALDH2) is a mitochondrial enzyme with some promises in a number of cardiovascular diseases. This study was designed to evaluate the impact of ALDH2 on cardiac remodeling and contractile property in high fat diet-induced obesity. METHODS: Wild-type (WT) and ALDH2 transgenic mice were fed low (10% calorie from fat) or high (45% calorie from fat) fat diet for 5 months prior to the assessment of cardiac geometry and function using echocardiography, IonOptix system, Lectin, and Masson Trichrome staining...
March 13, 2018: International Journal of Obesity: Journal of the International Association for the Study of Obesity
Vincenzo Carafa, Angela Nebbioso, Francesca Cuomo, Dante Rotili, Gilda Cobellis, Paola Bontempo, Alfonso Baldi, Enrico P Spugnini, Gennaro Citro, Angela Chambery, Rosita Russo, Menotti Ruvo, Paolo Ciana, Luca Maravigna, Jani Shaik, Enrico Radaelli, Pasqualino De Antonellis, Domenico Tarantino, Adele Pirolli, Rino Ragno, Massimo Zollo, Hendrik G Stunnenberg, Antonello Mai, Lucia Altucci
PURPOSE: Alteration in cell death is a hallmark of cancer. A functional role regulating survival, apoptosis and necroptosis has been attributed to RIP1/3 complexes. EXPERIMENTAL DESIGN: We have investigated the role of RIP1 and the effects of MC2494 in cell death induction, using different methods as flow cytometry, transcriptome analysis, immunoprecipitation, enzymatic assays, transfections, mutagenesis and in vivo studies with different mice models. RESULTS: Here, we show that RIP1 is highly expressed in cancer and we define a novel RIP1/3-SIRT1/2-HAT1/4 complex...
March 13, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
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