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https://www.readbyqxmd.com/read/27903254/mir-96-mir-145-and-mir-9-expression-increases-and-igf-1r-and-foxo1-expression-decreases-in-peripheral-blood-mononuclear-cells-of-aging-humans
#1
Monika Budzinska, Magdalena Owczarz, Eliza Pawlik-Pachucka, Malgorzata Roszkowska-Gancarz, Przemyslaw Slusarczyk, Monika Puzianowska-Kuznicka
BACKGROUND: In mammals, the IGF-1 pathway affects the phenotype of aging. Since the function of the immune system is modulated by IGF-1, it is plausible that immunosenescence might in part result from altered control by this pathway. We therefore examined whether the expression of IGF-1R, FOXO1, and FOXO3a in peripheral blood mononuclear cells (PBMC) changes with age and if this might be due to changes in the expression of select miRNAs. METHODS: The expression of IGF-1R, FOXO1, FOXO3a, as well as of miR-9, miR-96, miR-99a, miR-132, miR-145, and miR-182 was examined in PBMC of young (27...
November 30, 2016: BMC Geriatrics
https://www.readbyqxmd.com/read/27901267/binge-alcohol-intake-after-hypergravity-stress-sustainably-decreases-ampk-and-transcription-factors-necessary-for-hepatocyte-survival
#2
Sang Gil Lee, Hong Min Wu, Chan Gyu Lee, Choong Sik Oh, So Won Chung, Sang Geon Kim
BACKGROUND: Binge alcohol consumption elicits mitochondrial dysfunction in hepatocytes. An understanding of the effect of ethanol (EtOH) exposure after hypergravity stress on liver function may assist in the implementation of pathophysiological countermeasures for aerospace missions. This study investigated whether a combination of hypergravity stress and binge alcohol intake has a detrimental effect on AMP-activated protein kinase (AMPK) and other molecules necessary for hepatocyte survival...
November 30, 2016: Alcoholism, Clinical and Experimental Research
https://www.readbyqxmd.com/read/27897403/new-genetic-signatures-associated-with-cancer-cachexia-as-defined-by-low-skeletal-muscle-index-and-weight-loss
#3
Neil Johns, Cynthia Stretch, Benjamin H L Tan, Tora S Solheim, Sveinung Sørhaug, Nathan A Stephens, Ioannis Gioulbasanis, Richard J E Skipworth, D A Christopher Deans, Antonio Vigano, James A Ross, Oliver F Bathe, Michel L Tremblay, Stein Kaasa, Florian Strasser, Bruno Gagnon, Vickie E Baracos, Sambasivarao Damaraju, Kenneth C H Fearon
BACKGROUND: Cachexia affects the majority with advanced cancer. Based on current demographic and clinical factors, it is not possible to predict who will develop cachexia or not. Such variation may, in part, be due to genotype. It has recently been proposed to extend the diagnostic criteria for cachexia to include a direct measure of low skeletal muscle index (LSMI) in addition to weight loss (WL). We aimed to explore our panel of candidate single nucleotide polymorphism (SNPs) for association with WL +/- computerized tomography-defined LSMI...
August 5, 2016: Journal of Cachexia, Sarcopenia and Muscle
https://www.readbyqxmd.com/read/27896567/foxo1-and-lxr%C3%AE-downregulate-the-apolipoprotein-a-i-gene-expression-during-hydrogen-peroxide-induced-oxidative-stress-in-hepg2-cells
#4
Vladimir S Shavva, Alexandra M Bogomolova, Artemy A Nikitin, Ella B Dizhe, Galina N Oleinikova, Ivan A Lapikov, Dmitry A Tanyanskiy, Andrej P Perevozchikov, Sergey V Orlov
Reactive oxygen species damage various cell components including DNA, proteins, and lipids, and these impairments could be a reason for severe human diseases including atherosclerosis. Forkhead box O1 (FOXO1), an important metabolic transcription factor, upregulates antioxidant and proapoptotic genes during oxidative stress. Apolipoprotein A-I (ApoA-I) forms high density lipoprotein (HDL) particles that are responsible for cholesterol transfer from peripheral tissues to liver for removal in bile in vertebrates...
November 28, 2016: Cell Stress & Chaperones
https://www.readbyqxmd.com/read/27895178/conserved-region-c-functions-to-regulate-pd-1-expression-and-subsequent-cd8-t-cell-memory
#5
Alexander P R Bally, Yan Tang, Joshua T Lee, Benjamin G Barwick, Ryan Martinez, Brian D Evavold, Jeremy M Boss
Expression of programmed death 1 (PD-1) on CD8 T cells promotes T cell exhaustion during chronic Ag exposure. During acute infections, PD-1 is transiently expressed and has the potential to modulate CD8 T cell memory formation. Conserved region C (CR-C), a promoter proximal cis-regulatory element that is critical to PD-1 expression in vitro, responds to NFATc1, FoxO1, and/or NF-κB signaling pathways. Here, a CR-C knockout mouse was established to determine its role on PD-1 expression and the corresponding effects on T cell function in vivo...
November 28, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/27893611/absence-of-mir-182-augments-cardiac-allograft-survival
#6
Liang Wei, Vandana Kaul, Xiumei Qu, Xiaoxing Xiong, Audrey H Lau, Naoharu Iwai, Olivia M Martinez, Sheri M Krams
BACKGROUND: MicroRNAs (miRNAs) are small noncoding RNA molecules that regulate the posttranscriptional expression of target genes and are important regulators in immune responses. Previous studies demonstrated that the miRNA, miR-182 was significantly increased during allograft rejection. Further, the transcription factor Forkhead box (FOX) protein 1, (FOXO1) was shown to be a target of miR-182. The aim of this study is to further examine the role of miR-182 in alloimmune responses. METHODS: Transplantation of BALB/c cardiac allografts was performed in C57BL/6, miR-182, B6...
November 23, 2016: Transplantation
https://www.readbyqxmd.com/read/27880903/mirnas-are-essential-for-the-regulation-of-the-pi3k-akt-foxo-pathway-and-receptor-editing-during-b%C3%A2-cell-maturation
#7
Maryaline Coffre, David Benhamou, David Rieß, Lili Blumenberg, Valentina Snetkova, Marcus J Hines, Tirtha Chakraborty, Sofia Bajwa, Kari Jensen, Mark M W Chong, Lelise Getu, Gregg J Silverman, Robert Blelloch, Dan R Littman, Dinis Calado, Doron Melamed, Jane A Skok, Klaus Rajewsky, Sergei B Koralov
B cell development is a tightly regulated process dependent on sequential rearrangements of immunoglobulin loci that encode the antigen receptor. To elucidate the role of microRNAs (miRNAs) in the orchestration of B cell development, we ablated all miRNAs at the earliest stage of B cell development by conditionally targeting the enzymes critical for RNAi in early B cell precursors. Absence of any one of these enzymes led to a block at the pro- to pre-B cell transition due to increased apoptosis and a failure of pre-B cells to proliferate...
November 22, 2016: Cell Reports
https://www.readbyqxmd.com/read/27880728/analysis-of-mirna-profiles-identified-mir-196a-as-a-crucial-mediator-of-aberrant-pi3k-akt-signaling-in-lung-cancer-cells
#8
Ilaria Guerriero, Daniela D'Angelo, Pierlorenzo Pallante, Mafalda Santos, Marianna Scrima, Donatella Malanga, Carmela De Marco, Maria Ravo, Alessandro Weisz, Carmelo Laudanna, Michele Ceccarelli, Geppino Falco, Antonia Rizzuto, Giuseppe Viglietto
Hyperactivation of the PI3K/AKT pathway is observed in most human cancer including lung carcinomas. Here we have investigated the role of miRNAs as downstream targets of activated PI3K/AKT signaling in Non Small Cell Lung Cancer (NSCLC). To this aim, miRNA profiling was performed in human lung epithelial cells (BEAS-2B) expressing active AKT1 (BEAS-AKT1-E17K), active PI3KCA (BEAS-PIK3CA-E545K) or with silenced PTEN (BEAS-shPTEN).Twenty-four differentially expressed miRNAs common to BEAS-AKT1-E17K, BEAS-PIK3CA-E545K and BEAS-shPTEN cells were identified through this analysis, with miR-196a being the most consistently up-regulated miRNA...
November 17, 2016: Oncotarget
https://www.readbyqxmd.com/read/27880725/mouse-sirt3-promotes-autophagy-in-angii-induced-myocardial-hypertrophy-through-the-deacetylation-of-foxo1
#9
Jingyuan Li, Tongshuai Chen, Ming Xiao, Na Li, Shujian Wang, Hongyan Su, Xiaobin Guo, Hui Liu, Fangying Yan, Yi Yang, Yun Zhang, Peili Bu
Sirt3, a mitochondrial NAD+-dependent histone deacetylase, is the only member proven to promote longevity in mammalian Sirtuin family. The processed short form of Sirt3 has been demonstrated to target many mediators of energy metabolism and mitochondrial stress adaptive program. Autophagy serves as a dynamic recycling mechanism and provides energy or metabolic substrates. Among the mechanisms triggered by cardiac stress, opinions vary as to whether autophagy is a protective or detrimental response. Here, by inducing the Sirt3-knockout mice to myocardial hypertrophy with chronic angiotensin II infusion for four weeks, we determined the role of Sirt3 in myocardial hypertrophy and autophagy...
November 17, 2016: Oncotarget
https://www.readbyqxmd.com/read/27878235/accelerated-cell-cycle-progression-of-human-regulatory-t%C3%A2-cell-like-cell-line-caused-by-continuous-exposure-to-asbestos-fibers
#10
Suni Lee, Hidenori Matsuzaki, Megumi Maeda, Shoko Yamamoto, Naoko Kumagai-Takei, Tamayo Hatayama, Miho Ikeda, Kei Yoshitome, Yasumitsu Nishimura, Takemi Otsuki
Asbestos exposure causes malignant tumors such as lung cancer and malignant mesothelioma. Based on our hypothesis in which continuous exposure to asbestos of immune cells cause reduction of antitumor immunity, the decrease of natural killer cell killing activity with reduction of NKp46 activating receptor expression, inhibition of cytotoxic T cell clonal expansion, reduced CXCR3 chemokine receptor expression and production of interferon-γ production in CD4+ T cells were reported using cell line models, freshly isolated peripheral blood immune cells from health donors as well as asbestos exposed patients such as pleural plaque and mesothelioma...
November 22, 2016: International Journal of Oncology
https://www.readbyqxmd.com/read/27875996/differences-in-the-skeletal-muscle-transcriptome-profile-associated-with-extreme-values-of-fatty-acids-content
#11
Aline S M Cesar, Luciana C A Regitano, Mirele D Poleti, Sónia C S Andrade, Polyana C Tizioto, Priscila S N Oliveira, Andrezza M Felício, Michele L do Nascimento, Amália S Chaves, Dante P D Lanna, Rymer R Tullio, Renata T Nassu, James E Koltes, Eric Fritz-Waters, Gerson B Mourão, Adhemar Zerlotini-Neto, James M Reecy, Luiz L Coutinho
BACKGROUND: Lipids are a class of molecules that play an important role in cellular structure and metabolism in all cell types. In the last few decades, it has been reported that long-chain fatty acids (FAs) are involved in several biological functions from transcriptional regulation to physiological processes. Several fatty acids have been both positively and negatively implicated in different biological processes in skeletal muscle and other tissues. To gain insight into biological processes associated with fatty acid content in skeletal muscle, the aim of the present study was to identify differentially expressed genes (DEGs) and functional pathways related to gene expression regulation associated with FA content in cattle...
November 22, 2016: BMC Genomics
https://www.readbyqxmd.com/read/27872010/forkhead-box-o1-in-grass-carp-ctenopharyngodon-idella-molecular-characterization-gene-structure-tissue-distribution-and-mrna-expression-in-insulin-inhibited-adipocyte-lipolysis
#12
Jian Sun, Pei-Zhen Xiao, Zhi-Guang Chang, Hong Ji, Zhen-Yu Du, Li-Qiao Chen
Factor forkhead box O1 (FoxO1) is a transcription factor and plays an important role in insulin-mediated lipid metabolism. In the present study, two distinct FoxO1 cDNAs, designated FoxO1a and FoxO1b, were firstly isolated and characterized from grass carp Ctenopharyngodon idella, encoding peptides of 654 and 631 amino acids, respectively. Phylogenetic and synteny analyses suggested that FoxO1a and FoxO1b were derived from paralogous genes that could be originated from teleost-specific genome duplication (TSGD) event...
November 18, 2016: Comparative Biochemistry and Physiology. Part A, Molecular & Integrative Physiology
https://www.readbyqxmd.com/read/27861641/pdcd2l-promotes-palmitate-induced-pancreatic-beta-cell-apoptosis-as-a-foxo1-target-gene
#13
Ye Yin, Wei Yong, Jiani Yu, Xu Zhang, Haiyan Lin, Yunxia Zhu, Xiao Han
Transcription factor FoxO1 is a key regulator of the insulin-signaling pathway, and is reported to play important roles in pancreatic β cell differentiation, proliferation, apoptosis and stress resistance. The multifunctional nature of FoxO1 is due to its regulation of various downstream targets. Previous studies in our lab identified potential FoxO1 target genes using the ChIP-DSL technique and one of those genes, Pdcd2l, was selected for further study. We found that the expression of Pdcd2l was increased with palmitate treatment; the luciferase assay result revealed that enhanced Pdcd2l promoter activity was responsible for the elevation of Pdcd2l expression...
2016: PloS One
https://www.readbyqxmd.com/read/27853183/exosomes-derived-from-embryonal-and-alveolar-rhabdomyosarcoma-carry-differential-mirna-cargo-and-promote-invasion-of-recipient-fibroblasts
#14
Sandra E Ghayad, Ghina Rammal, Farah Ghamloush, Hussein Basma, Rihab Nasr, Mona Diab-Assaf, Claude Chelala, Raya Saab
Rhabdomyosarcoma (RMS) is an aggressive childhood soft tissue tumor, which exists in oncoprotein PAX-FOXO1 fusion positive and fusion negative subtypes, with the fusion-positive RMS being characterized by a more aggressive clinical behavior. Exosomes are small membranous vesicles secreted into body fluids by multiple cell types, including tumor cells, and have been implicated in metastatic progression through paracrine signaling. We characterized exosomes secreted by a panel of 5 RMS cell lines. Expression array analysis showed that, for both fusion-positive and fusion-negative cells, exosome miRNA clustered well together and to a higher extent than cellular miRNA...
November 17, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27845161/downregulation-of-autophagy-gene-expression-in-endometria-from-women-with-polycystic-ovary-syndrome
#15
Mirjana Sumarac-Dumanovic, Milica Apostolovic, Kristina Janjetovic, Danka Jeremic, Dusan Popadic, Aleksandar Ljubic, Jelena Micic, Jelena Dukanac-Stamenkovic, Aleksandra Tubic, Darko Stevanovic, Dragan Micic, Vladimir Trajkovic
Autophagy, a process of controlled cellular self-digestion, could be involved in cyclic remodeling of the human endometrium. We investigated endometrial mRNA expression of 23 autophagy-related (ATG) genes and transcription factors in healthy controls (n = 12) and anovulatory polycystic ovary syndrome (PCOS) patients (n = 24), as well as in their subgroup (n = 12) before and after metformin treatment. The mRNA levels of transcription factor forkhead box protein O1 (FOXO1) and several molecules involved in autophagosome formation (ATG13, RB1-inducible coiled-coil 1), autophagosome nucleation (ATG14, beclin 1, SH3-domain GRB2-like endophilin B1), autophagosome elongation (ATG3, ATG5, γ-aminobutyric acid receptor-associated protein - GABARAP), and delivery of ubiquitinated proteins to autophagosomes (sequestosome 1), were significantly reduced in anovulatory PCOS compared to healthy endometrium...
November 11, 2016: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/27835585/transcriptional-repression-of-foxo1-by-klf4-contributes-to-glioma-progression
#16
Guodong Tang, Dingyang Liu, Gelei Xiao, Qing Liu, Jian Yuan
In this study, our findings indicated that FOXO1 expression frequently decreased in glioma tissues and cells. FOXO1 expression decrease correlated with glioma progression and predicted a worse overall survival of glioma patients. Restored FOXO1 expression inhibited glioma cells invasion and suppressed glioma cells proliferation in vitro and growth in vivo. Additionally, we found that KLF4 expression frequently increased in glioma tissues and negatively correlated with FOXO1 expression. Bioinformatics analysis and experimental results indicated that KLF4 transcriptionally repressed FOXO1 expression in glioma cells...
November 7, 2016: Oncotarget
https://www.readbyqxmd.com/read/27834289/the-metabolic-effects-of-prazosin-on-skeletal-muscle-insulin-resistance-in-glucocorticoid-treated-male-rats
#17
Emily C Dunford, Erin R Mandel, Sepideh Mohajeri, Tara L Haas, Michael C Riddell
High dose glucocorticoids (GC) induce skeletal muscle atrophy, insulin resistance and reduced muscle capillarization. Identification of treatments to prevent or reverse capillary rarefaction and metabolic deterioration caused by prolonged elevations in GCs would be therapeutically beneficial. Chronic administration of prazosin, α1-adrenergic antagonist, increases skeletal muscle capillarization, in healthy rodents and recently, a rodent model of elevated GCs and hyperglycemia. The purpose of this study was to determine whether prazosin administration would improve glucose tolerance and insulin sensitivity, through prazosin mediated sparing of capillary rarefaction, in this rodent model of increased GC exposure...
November 9, 2016: American Journal of Physiology. Regulatory, Integrative and Comparative Physiology
https://www.readbyqxmd.com/read/27820700/the-transcription-factor-nr4a3-controls-cd103-dendritic-cell-migration
#18
Kiwon Park, Zbigniew Mikulski, Goo-Young Seo, Aleksander Y Andreyev, Paola Marcovecchio, Amy Blatchley, Mitchell Kronenberg, Catherine C Hedrick
The transcription factor NR4A3 (also known as NOR-1) is a member of the Nr4a family of nuclear receptors and is expressed in myeloid and lymphoid cells. Here, we have shown that Nr4a3 is essential for the migration of CD103+ dendritic cells (DCs) to lymph nodes (LNs). Nr4a3-deficient mice had very few CD103+ migratory DCs (mDCs) present in LNs, and mixed-chimera studies revealed that this migratory defect was cell intrinsic. We further found that CD103+ DCs from Nr4a3-deficient mice displayed a marked loss of surface expression of the chemokine CCR7...
December 1, 2016: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/27816669/the-bank1-sle-risk-variants-are-associated-with-alterations-in-peripheral-b-cell-signaling-and-development-in-humans
#19
Elizabeth M Dam, Tania Habib, Janice Chen, Andrew Funk, Veronika Glukhova, Mel Davis-Pickett, Shan Wei, Richard James, Jane H Buckner, Karen Cerosaletti
Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized by the development of autoantibodies that drive disease pathogenesis. Genetic studies have associated nonsynonymous variants in the BANK1 B cell scaffolding gene with susceptibility to SLE and autoantibodies in lupus. To determine how the BANK1 SLE-risk variants contribute to the dysregulated B cell program in lupus, we performed genotype/phenotype studies in human B cells. Targeted phospho-proteomics were used to evaluate BCR/CD40 signaling in human B cell lines engineered to express the BANK1 risk or non-risk variant proteins...
November 2, 2016: Clinical Immunology: the Official Journal of the Clinical Immunology Society
https://www.readbyqxmd.com/read/27815072/the-transcription-factor-prep1-controls-hepatic-insulin-sensitivity-and-gluconeogenesis-by-targeting-nuclear-localization-of-foxo1
#20
Konstantin Kulebyakin, Dmitry Penkov, Francesco Blasi, Zhanna Akopyan, Vsevolod Tkachuk
Liver plays a key role in controlling body carbohydrate homeostasis by switching between accumulation and production of glucose and this way maintaining constant level of glucose in blood. Increased blood glucose level triggers release of insulin from pancreatic β-cells. Insulin represses hepatic glucose production and increases glucose accumulation. Insulin resistance is the main cause of type 2 diabetes and hyperglycemia. Currently thiazolidinediones (TZDs) targeting transcriptional factor PPARγ are used as insulin sensitizers for treating patients with type 2 diabetes...
December 2, 2016: Biochemical and Biophysical Research Communications
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