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https://www.readbyqxmd.com/read/28224334/the-trpm4-channel-is-functionally-important-for-the-beneficial-cardiac-remodeling-induced-by-endurance-training
#1
Mélanie Gueffier, Justin Zintz, Karen Lambert, Amanda Finan, Franck Aimond, Nourdine Chakouri, Christophe Hédon, Mathieu Granier, Pierre Launay, Jérôme Thireau, Sylvain Richard, Marie Demion
Cardiac hypertrophy (CH) is an adaptive process that exists in two distinct forms and allows the heart to adequately respond to an organism's needs. The first form of CH is physiological, adaptive and reversible. The second is pathological, irreversible and associated with fibrosis and cardiomyocyte death. CH involves multiple molecular mechanisms that are still not completely defined but it is now accepted that physiological CH is associated more with the PI3-K/Akt pathway while the main signaling cascade activated in pathological CH involves the Calcineurin-NFAT pathway...
February 21, 2017: Journal of Muscle Research and Cell Motility
https://www.readbyqxmd.com/read/28196514/defining-the-contribution-of-neuroinflammation-to-parkinson-s-disease-in-humanized-immune-system-mice
#2
Gunjan Dhawan Manocha, Angela Marie Floden, Kendra Lynn Puig, Kumi Nagamoto-Combs, Clemens R Scherzer, Colin Kelly Combs
BACKGROUND: Reactive microglia have been associated with the histological changes that occur in Parkinson's disease brains and mouse models of the disease. Multiple studies from autopsy brains have verified the presence of microgliosis in several brain regions including substantia nigra, striatum, hippocampus and various cortical areas. MPTP injections in rodents have also shown striato-nigral microgliosis correlating with the loss of dopaminergic neurons. However, consistent data with respect to cytokine and immune cell changes during Parkinson's disease have not been fully defined...
February 14, 2017: Molecular Neurodegeneration
https://www.readbyqxmd.com/read/28188290/activated-cdc42-associated-kinase-1-ack1-binds-the-sam-domain-of-adaptor-slp-76-and-phosphorylates-proximal-tyrosines
#3
Youg R Thaker, Asha Recino, Monika Raab, Asma Jabeen, Maja Wallberg, Nelson Fernandez, Christopher E Rudd
The adaptor protein Src homology 2 domain-containing leukocyte phospho-protein of 76 kDa (SLP-76) plays a crucial role in T-cell activation by linking antigen receptor (TCR) signals to downstream pathways. At its N-terminus, SLP-76 has three key N-terminus tyrosines (Y113, Y128 and Y145, or 3Y) as well as a sterile-α motif (SAM) domain, whose function is unclear. We previously showed that the SAM domain has two binding regions that mediate dimer and oligomer formation. In this study, we have identified SAM domain-carrying non-receptor tyrosine kinase, activated Cdc42-associated tyrosine kinase 1 (ACK1; also known as Tnk2, tyrosine kinase non receptor 2), as a novel binding partner of SLP-76...
February 10, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28183532/growth-factor-midkine-promotes-nuclear-factor-of-activated-t-cells-regulated-t-cell-activation-and-th1-cell-differentiation-in-lupus-nephritis
#4
Tomohiro Masuda, Kayaho Maeda, Waichi Sato, Tomoki Kosugi, Yuka Sato, Hiroshi Kojima, Noritoshi Kato, Takuji Ishimoto, Naotake Tsuboi, Kenji Uchimura, Yukio Yuzawa, Shoichi Maruyama, Kenji Kadomatsu
Activated T cells play crucial roles in the pathogenesis of autoimmune diseases, including lupus nephritis (LN). The activation of calcineurin/nuclear factor of activated T cells (NFAT) and STAT4 signaling is essential for T cells to perform various effector functions. Here, we identified the growth factor midkine (MK; gene name, Mdk) as a novel regulator in the pathogenesis of 2,6,10,14-tetramethylpentadecane-induced LN via activation of NFAT and IL-12/STAT4 signaling. Wild-type (Mdk(+/+)) mice showed more severe glomerular injury than MK-deficient (Mdk(-/-)) mice, as demonstrated by mesangial hypercellularity and matrix expansion, and glomerular capillary loops with immune-complex deposition...
February 7, 2017: American Journal of Pathology
https://www.readbyqxmd.com/read/28183531/cardiomyocyte-hypertrophy-in-arrhythmogenic-cardiomyopathy
#5
Mustafa Gerçek, Muhammed Gerçek, Sebastian Kant, Sakine Simsekyilmaz, Astrid Kassner, Hendrik Milting, Elisa A Liehn, Rudolf E Leube, Claudia A Krusche
Arrhythmogenic cardiomyopathy (AC) is a hereditary disease leading to sudden cardiac death or heart failure. AC pathology is characterized by cardiomyocyte loss and replacement fibrosis. Our goal was to determine whether cardiomyocytes respond to AC progression by pathological hypertrophy. To this end, we examined tissue samples from AC patients with end-stage heart failure and tissue samples that were collected at different disease stages from desmoglein 2-mutant mice, a well characterized AC model. We find that cardiomyocyte diameters are significantly increased in right ventricles of AC patients...
February 6, 2017: American Journal of Pathology
https://www.readbyqxmd.com/read/28165497/wnt7a-inhibits-il-1%C3%AE-induced-catabolic-gene-expression-and-prevents-articular-cartilage-damage-in-experimental-osteoarthritis
#6
Averi L Gibson, Carrie K Hui Mingalone, Andrea T Foote, Tomoya Uchimura, Ming Zhang, Li Zeng
Wnt7a is a protein that plays a critical role in skeletal development. However, its effect on cartilage homeostasis under pathological conditions is not known. In this study, we found a unique inverse correlation between Wnt7a gene expression and that of MMP and IL-1β in individual human OA cartilage specimens. Upon ectopic expression in primary human articular chondrocytes, Wnt7a inhibited IL-1β-induced MMP and iNOS gene expression. Western blot analysis indicated that Wnt7a induced both canonical Wnt signaling and NFAT and Akt non-canonical signaling...
February 6, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28153703/cross-talk-among-pmca-calcineurin-and-nfat-transcription-factors-in-control-of-calmodulin-gene-expression-in-differentiating-pc12-cells
#7
Tomasz Boczek, Malwina Lisek, Bozena Ferenc, Ludmila Zylinska
Brain aging is characterized by progressive loss of plasma membrane calcium pump (PMCA) and its activator - calmodulin (CaM), but the mechanism of this phenomenon remains unresolved. CaM encoded by three genes Calm1, Calm2, Calm3, works to translate Ca(2+) signal into changes in frequently opposite cellular activities. This unique function allows CaM to affect gene expression via stimulation of calcineurin (CaN) and its downstream target - nuclear factor of activated T-cells (NFAT) and to terminate Ca(2+) signal by stimulation of its extrusion...
January 30, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28153342/calcium-nfat-transcriptional-signalling-in-t-cell-activation-and-t-cell-exhaustion
#8
REVIEW
Patrick G Hogan
A cornerstone of the adaptive immune response is the T cell receptor (TcR)-calcium-calcineurin signalling pathway leading to T cell activation. The 'nuclear factor of activated T cells' proteins NFAT1, NFAT2, and NFAT4 are transcription factors that promote expression of a panel of genes required for activation. It has become apparent that these same NFAT transcription factors underlie an alternative transcriptional program in T cells that serves to limit the immune response. This duality in NFAT transcriptional functions raises the possibility that NFAT transcriptional complexes could be targeted therapeutically to alter the relative strength of the effector and alternative transcriptional programs, thereby modulating immune responses...
January 28, 2017: Cell Calcium
https://www.readbyqxmd.com/read/28130342/nfat-regulation-of-cystathionine-gamma-lyase-expression-in-endothelial-cells-is-impaired-in-rats-exposed-to-intermittent-hypoxia
#9
Laura V Gonzalez Bosc, Jessica M Osmond, Wieslawa Giermakowska, Carolyn E Pace, Jennifer L Riggs, Olan Jackson-Weaver, Nancy L Kanagy
Sleep apnea is a risk factor for cardiovascular disease, and intermittent hypoxia (IH, 20 episodes/hr of 5% O2/5% CO2 for 7 hr/day) to mimic sleep apnea increases blood pressure and impairs H2S-induced vasodilation in rats. The enzyme that produces H2S, cystathionine gamma lyase (CSE), is decreased in rat mesenteric artery endothelial cells (EC) following in vivo IH exposure. In silico analysis identified putative NFAT binding sites in the CSE promoter. Therefore, we hypothesized that IH exposure reduces [Ca(2+)] activation of calcineurin/NFAT to lower CSE expression and impairs vasodilation...
January 27, 2017: American Journal of Physiology. Heart and Circulatory Physiology
https://www.readbyqxmd.com/read/28125639/nfatc3-and-vip-in-idiopathic-pulmonary-fibrosis-and-chronic-obstructive-pulmonary-disease
#10
Anthony M Szema, Edward Forsyth, Benjamin Ying, Sayyed A Hamidi, John J Chen, Sonya Hwang, Jonathan C Li, Debra Sabatini Dwyer, Juan M Ramiro-Diaz, Wieslawa Giermakowska, Laura V Gonzalez Bosc
Idiopathic pulmonary fibrosis (IPF) and chronic obstructive pulmonary disease (COPD) are both debilitating lung diseases which can lead to hypoxemia and pulmonary hypertension (PH). Nuclear Factor of Activated T-cells (NFAT) is a transcription factor implicated in the etiology of vascular remodeling in hypoxic PH. We have previously shown that mice lacking the ability to generate Vasoactive Intestinal Peptide (VIP) develop spontaneous PH, pulmonary arterial remodeling and lung inflammation. Inhibition of NFAT attenuated PH in these mice suggesting a connection between NFAT and VIP...
2017: PloS One
https://www.readbyqxmd.com/read/28108285/rifampin-suppresses-osteoclastogenesis-and-titanium-particle-induced-osteolysis-via-modulating-rankl-signaling-pathways
#11
Liang Zhu, Hui Kang, Chang-An Guo, Wen-Shuai Fan, Yi-Ming Wang, Lian-Fu Deng, Zuo-Qin Yan
Wear particles liberated from the surface of prostheses are considered to be main reason for osteoclast bone resorption and that extensive osteoclastogenesis leads to peri-implant osteolysis and subsequent prosthetic loosening. The aim of this study was to assess the effect of rifampin on osteoclastogenesis and titanium (Ti) particle-induced osteolysis. The Ti particle-induced osteolysis mouse calvarial model and bone marrow-derived macrophages (BMMs) were used. Rifampin, at dose of 10 or 50 mg/kg/day, was respectively given intraperitoneally for 14 days in vivo...
January 18, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28106828/bajijiasu-abrogates-osteoclast-differentiation-via-the-suppression-of-rankl-signaling-pathways-through-nf-%C3%AE%C2%BAb-and-nfat
#12
Guoju Hong, Lin Zhou, Xuguang Shi, Wei He, Haibin Wang, Qiushi Wei, Peng Chen, Longkai Qi, Jennifer Tickner, Li Lin, Jiake Xu
Pathological osteolysis is commonly associated with osteoporosis, bone tumors, osteonecrosis, and chronic inflammation. It involves excessive resorption of bone matrix by activated osteoclasts. Suppressing receptor activator of NF-κB ligand (RANKL) signaling pathways has been proposed to be a good target for inhibiting osteoclast differentiation and bone resorption. Bajijiasu-a natural compound derived from Morinda officinalis F. C. How-has previously been shown to have anti-oxidative stress property; however, its effect and molecular mechanism of action on osteoclastogenesis and bone resorption remains unclear...
January 19, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28103134/the-role-of-nuclear-factor-of-activated-t-cells-in-pulmonary-arterial-hypertension
#13
Rui Chen, Jinchuan Yan, Peijing Liu, Zhongqun Wang, Cuiping Wang, Wei Zhong, Liangjie Xu
Nuclear factor of activated T cells (NFAT) was first identified as a transcription factor about three decades ago and was not well studied until the development of immunosuppressant. Numerous studies confirm that calcineurin/NFAT signaling is very important in the development of vasculature and cardiovascular system during embryogenesis and is involved in the development of vascular diseases such as hypertension, atherosclerosis and restenosis. Recent studies demonstrated that NFAT proteins also regulate immune response and vascular cells in the pulmonary microenvironment...
January 19, 2017: Cell Cycle
https://www.readbyqxmd.com/read/28100021/identifying-the-biphasic-role-of-calcineurin-nfat-signaling-enables-replacement-of-sox2-in-somatic-cell-reprogramming
#14
Sherif Khodeer, Takumi Era
Induction of pluripotency with defined factors (Oct4, Sox2, Klf4, c-Myc) raises hopes for successful clinical trials. Despite considerable efforts, the molecular mechanism of reprogramming remains poorly understood. The aim of the present study was to identify the role of calcineurin/nuclear factor of activated T cells (NFAT) in reprogramming. Our results demonstrated a biphasic role for calcineurin/NFAT signaling during reprogramming. In the early phase of reprogramming, calcineurin activity is required to maintain proper cell cycle division and for mesenchymal-epithelial transition...
January 18, 2017: Stem Cells
https://www.readbyqxmd.com/read/28062691/activating-mutations-and-translocations-in-the-guanine-exchange-factor-vav1-in-peripheral-t-cell-lymphomas
#15
Francesco Abate, Ana C da Silva-Almeida, Sakellarios Zairis, Javier Robles-Valero, Lucile Couronne, Hossein Khiabanian, S Aidan Quinn, Mi-Yeon Kim, Maria Antonella Laginestra, Christine Kim, Danilo Fiore, Govind Bhagat, Miguel Angel Piris, Elias Campo, Izidore S Lossos, Olivier A Bernard, Giorgio Inghirami, Stefano Pileri, Xosé R Bustelo, Raul Rabadan, Adolfo A Ferrando, Teresa Palomero
Peripheral T-cell lymphomas (PTCLs) are a heterogeneous group of non-Hodgkin lymphomas frequently associated with poor prognosis and for which genetic mechanisms of transformation remain incompletely understood. Using RNA sequencing and targeted sequencing, here we identify a recurrent in-frame deletion (VAV1 Δ778-786) generated by a focal deletion-driven alternative splicing mechanism as well as novel VAV1 gene fusions (VAV1-THAP4, VAV1-MYO1F, and VAV1-S100A7) in PTCL. Mechanistically these genetic lesions result in increased activation of VAV1 catalytic-dependent (MAPK, JNK) and non-catalytic-dependent (nuclear factor of activated T cells, NFAT) VAV1 effector pathways...
January 24, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28062573/deficiency-of-n-myristoylation-reveals-calcineurin-activity-as-regulator-of-ifn-%C3%AE-producing-%C3%AE-%C3%AE-t-cells
#16
Francesca Rampoldi, Fabian Brunk, Mahnaz Bonrouhi, Giuseppina Federico, Damir Krunic, Stefan Porubsky, Hermann-Josef Gröne, Zoran V Popovic
γδ T cell subsets can be characterized, in part, by their secretion of select proinflammatory cytokines. The molecular mechanisms driving the diverse fates of γδ T cells have not been elucidated. We have previously shown that the attachment of myristic acid to the N-terminal glycine of proteins, termed N-myristoylation, is essential for αβ T cell development and activation. Here, we explore the potential role of this lipid modification on the activation of γδ T cells. In the absence of N-myristoylation, the CD27(+) γδ T cell subset was dominantly affected...
January 6, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28058586/key-genes-in-stomach-adenocarcinoma-identified-via-network-analysis-of-rna-seq-data
#17
Li Shen, Lizhi Zhao, Jiquan Tang, Zhiwei Wang, Weisong Bai, Feng Zhang, Shouli Wang, Weihua Li
RNA-seq data of stomach adenocarcinoma (STAD) were analyzed to identify critical genes in STAD. Meanwhile, relevant small molecule drugs, transcription factors (TFs) and microRNAs (miRNAs) were also investigated. Gene expression data of STAD were downloaded from The Cancer Genome Atlas (TCGA). Differential analysis was performed with package edgeR. Relationships with correlation coefficient > 0.6 were retained in the gene co-expression network. Functional enrichment analysis was performed for the genes in the network with DAVID and KOBASS 2...
January 5, 2017: Pathology Oncology Research: POR
https://www.readbyqxmd.com/read/28056508/fk506-an-immunosuppressive-drug-induces-autophagy-by-binding-to-the-v-atpase-catalytic-subunit-a-in-neuronal-cells
#18
Dongyoung Kim, Hui-Yun Hwang, Jin Young Kim, Ju Yeon Lee, Jong Shin Yoo, György Marko-Varga, Ho Jeong Kwon
The drug FK506 (tacrolimus, fujimycin) exerts its immunosuppressive effects by regulating the nuclear factor of the activated T-cell (NFAT) family of transcription factors. However, FK506 also exhibits neuroprotective effects, but its direct target proteins that mediate these effects have not been determined. To identify the target proteins responsible for FK506's neuroprotective effects, the drug affinity responsive target stability (DARTS) method was performed using label-free FK506, and LC-MS/MS analysis of the FK506-treated proteome was also performed...
January 6, 2017: Journal of Proteome Research
https://www.readbyqxmd.com/read/28027307/population-heterogeneity-in-the-epithelial-to-mesenchymal-transition-is-controlled-by-nfat-and-phosphorylated-sp1
#19
Russell Gould, David M Bassen, Anirikh Chakrabarti, Jeffrey D Varner, Jonathan Butcher
Epithelial to mesenchymal transition (EMT) is an essential differentiation program during tissue morphogenesis and remodeling. EMT is induced by soluble transforming growth factor β (TGF-β) family members, and restricted by vascular endothelial growth factor family members. While many downstream molecular regulators of EMT have been identified, these have been largely evaluated individually without considering potential crosstalk. In this study, we created an ensemble of dynamic mathematical models describing TGF-β induced EMT to better understand the operational hierarchy of this complex molecular program...
December 2016: PLoS Computational Biology
https://www.readbyqxmd.com/read/28025957/correlation-between-pharmacokinetics-of-tacrolimus-and-pharmacodynamics-on-nfat-regulated-gene-expression-in-stable-kidney-transplant-recipients%C3%A2
#20
Frieder Keller, Claudia Sommerer, Thomas Giese, Martin Zeier, Bernd Schröppel
Gene expression regulated by the transcription factor NFAT (nuclear factor of activated T-cells) has been proposed for monitoring the pharmacodynamic effect of calcineurin inhibitors. We aimed to correlate the pharmacokinetics of tacrolimus with the suppression of NFAT-regulated gene expression. Tacrolimus trough (C<sub>trough</sub>) and peak concentrations (C<sub>peak</sub>) were measured by LC-MS. The effect on NFAT-regulated gene expression at trough (E<sub>trough</sub>) and at peak levels (E<sub>peak</sub>) were determined by qRT-PCR...
February 2017: Clinical Nephrology
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