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https://www.readbyqxmd.com/read/29129565/human-papillomavirus-hpv-oncoprotein-e6-facilitates-calcineurin-nuclear-factor-for-activated-t-cells-2-nfat2-signaling-to-promote-cellular-proliferation-in-cervical-cell-carcinoma
#1
Babul Moni Ram, Jayashree Dolpady, Rakesh Kulkarni, R Usha, Usha Bhoria, Usha Rani Poli, Mojahidul Islam, Nirupma Trehanpati, Gayatri Ramakrishna
The calcineurin-NFAT signalling pathway regulates cell proliferation, differentiation, and development in diverse cell types and organ systems. Deregulation of calcineurin-NFAT signalling has been reported in leukaemias and few solid tumors such as breast and colon. In the present study, we found elevated calcineurin protein levels and phosphatase activity in cervical cancer cell lines and depletion of the same attenuated cell proliferation. Additionally, nuclear levels of NFAT2, a downstream target of calcineurin, viz, was found elevated in human papillomavirus (HPV) infected cells, HeLa and SiHa, compared to the HPV negative cells, HaCaT and C33A, indicative of its higher DNA binding activity...
November 9, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/29129208/augmented-gene-expression-triggered-by-na-k-atpase-inhibition-role-of-ca-2-i-mediated-and-independent-excitation-transcription-coupling
#2
Larisa V Smolyaninova, Svetlana V Koltsova, Svetlana V Sidorenko, Sergei N Orlov
In rat vascular smooth muscle cells (RVSMC), 3-h Na(+),K(+)-ATPase inhibition by ouabain or in K(+)-free medium resulted in the inversion of the [Na(+)]i/[K(+)]i ratio and elevation up to 7-fold the content of Egr1, Atf3, Nr4a1 and Ptgs2 mRNAs. Ouabain increased the rate of 45Ca(2+) influx by 2-fold that was abolished by L-type voltage-gated Ca(2+) channel blocker nicardipine, but it was resistant to Na(+)/Ca(2+) exchanger inhibitor KB-R7943. To study the role of Ca(2+)-mediated signaling in the expression of Na(+)i/K(+)i-sensitive genes we used intracellular Ca(2+) chelator BAPTA and incubated RVSMC in Ca(2+)-free medium...
December 2017: Cell Calcium
https://www.readbyqxmd.com/read/29124284/ca-2-nuclear-factor-of-activated-t-cells-signaling-is-enriched-in-early-onset-rectal-tumors-devoid-of-canonical-wnt-activation
#3
Raju Kumar, Ratheesh Raman, Viswakalyan Kotapalli, Swarnalata Gowrishankar, Saumyadipta Pyne, Jonathan R Pollack, Murali D Bashyam
Our previous extensive analysis revealed a significant proportion of early-onset colorectal tumors from India to be localized to the rectum in younger individuals and devoid of deregulated Wnt/β-catenin signaling. In the current study, we performed a comprehensive genome-wide analysis of clinically well-annotated microsatellite stable early-onset sporadic rectal cancer (EOSRC) samples. Results revealed extensive DNA copy number alterations in rectal tumors in the absence of deregulated Wnt/β-catenin signaling...
November 9, 2017: Journal of Molecular Medicine: Official Organ of the "Gesellschaft Deutscher Naturforscher und Ärzte"
https://www.readbyqxmd.com/read/29115003/impact-of-hypercortisolism-on-skeletal-muscle-mass-and-adipose-tissue-mass-in-patients-with-adrenal-adenomas
#4
Danae A Delivanis, Nicole M Iñiguez-Ariza, Muhammad H Zeb, Michael R Moynagh, Naoki Takahashi, Travis J McKenzie, Melinda A Thomas, Charalambos Gogos, William F Young, Irina Bancos, Venetsana Kyriazopoulou
CONTEXT: Abdominal visceral adiposity and central sarcopenia are markers of increased cardiovascular risk and mortality. OBJECTIVE: To assess whether central sarcopenia and adiposity can serve as a marker of disease severity in patients with adrenal adenomas and glucocorticoid secretory autonomy. DESIGN: Retrospective cohort study. PATIENTS: Twenty-five patients with overt Cushing syndrome (CS), 48 patients with mild autonomous cortisol excess (MACE), and 32 patients with a non-functioning adrenal tumor (NFAT) were included...
November 8, 2017: Clinical Endocrinology
https://www.readbyqxmd.com/read/29114247/elusive-role-of-the-cd94-nkg2c-nk-cell-receptor-in-the-response-to-cytomegalovirus-novel-experimental-observations-in-a-reporter-cell-system
#5
Aldi Pupuleku, Marcel Costa-García, Domènec Farré, Hartmut Hengel, Ana Angulo, Aura Muntasell, Miguel López-Botet
Human cytomegalovirus (HCMV) infection promotes the differentiation and persistent expansion of a mature NK cell subset, which displays high surface levels of the activating CD94/NKG2C NK cell receptor, together with additional distinctive phenotypic and functional features. The mechanisms underlying the development of adaptive NK cells remain uncertain but some observations support the involvement of a cognate interaction of CD94/NKG2C with ligand(s) displayed by HCMV-infected cells. To approach this issue, the heterodimer and its adaptor (DAP12) were expressed in the human Jurkat leukemia T cell line; signaling was detected by transfection of a reporter plasmid encoding for Luciferase (Luc) under NFAT/AP1-dependent control...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29107144/osteon-myospalacem-baileyi-attenuates-osteoclast-differentiation-through-rankl-induced-nfat-pathways
#6
Yulei Cui, Xiaoying Zhao, Lijuan Mei, Jinjin Pei, Shuo Wang, Yun Shao, Yanduo Tao, Xiaoling Zhang, Lei Jiang
ETHNOPHARMACOLOGICAL RELEVANCE: Osteon Myospalacem Baileyi, known as Sai long gu (Tibetan language, means "blind rat bone"), is the whole skeleton of Tibet plateau rodentia animal Myospalacem Baileyi. Osteon Myospalacem Baileyi had been widely used in the Tibet region as an anti-osteoporosis drug and since 1991 Osteon Myospalacem Baileyi has been listed in the Pharmacopoeia of People's Republic of China as the first-class animal new medical material. However, the mechanism of its anti-osteoporosis activities is still unclear...
October 26, 2017: Journal of Ethnopharmacology
https://www.readbyqxmd.com/read/29104875/a-novel-system-for-the-quantification-of-the-adcc-activity-of-therapeutic-antibodies
#7
Christophe Lallemand, Feifei Liang, Flore Staub, Maud Simansour, Benoit Vallette, Lue Huang, Rosa Ferrando-Miguel, Michael G Tovey
Novel ADCC effector cells expressing the V-variant or F-variant of FcγRIIIa (CD16a) and firefly luciferase under the control of a chimeric promoter incorporating recognition sequences for the principal transcription factors involved in FcγRIIIa signal transduction, together with novel target cells overexpressing a constant high level of the specific antigen recognized by rituximab, trastuzumab, cetuximab, infliximab, adalimumab, or etanercept, confer improved sensitivity, specificity, and dynamic range in an ADCC assay relative to effector cells expressing a NFAT-regulated reporter gene and wild-type target cells...
2017: Journal of Immunology Research
https://www.readbyqxmd.com/read/29104781/the-minor-variant-of-the-single-nucleotide-polymorphism-rs3753381-affects-the-activity-of-a-slamf1-enhancer
#8
L V Putlyaeva, A M Schwartz, A V Klepikova, I E Vorontsov, I V Kulakovskiy, D V Kuprash
The SLAMF1 gene encodes CD150, a transmembrane glycoprotein expressed on the surface of T and B-lymphocytes, NK-cells, dendritic cells, and subpopulations of macrophages and basophils. We investigated the functional regulatory polymorphisms of the SLAMF1 locus associated with autoimmune processes, using bioinformatics and a mutational analysis of the regulatory elements overlapping with polymorphic positions. In the reporter gene assay in MP-1 and Raji B-cell lines, the enhancer activity of the regulatory region of the locus containing the rs3753381 polymorphism demonstrated a twofold increase upon the introduction of the rs3753381 minor variant (G → A) associated with myasthenia gravis...
July 2017: Acta Naturae
https://www.readbyqxmd.com/read/29103109/polymorphisms-of-nucleotide-factor-of-activated-t-cells-cytoplasmic-2-and-4-and-the-risk-of-acute-rejection-following-kidney-transplantation
#9
Zijie Wang, Haiwei Yang, Shuhui Si, Zhijian Han, Jun Tao, Hao Chen, Yuqiu Ge, Miao Guo, Ke Wang, Ruoyun Tan, Ji-Fu Wei, Min Gu
BACKGROUND: Acute rejection (AR) is a common complication of kidney transplantation. Nuclear factors of activated T cells (NFATs) are transcription factors involved in the activation of T lymphocytes, but their association with AR is unclear. METHODS: This retrospective, case-control study included 200 renal transplant recipients who were divided into the AR group (n = 69) and stable group (n = 131). Their blood samples were collected, and DNA was extracted from the whole blood...
November 4, 2017: World Journal of Urology
https://www.readbyqxmd.com/read/29101238/glucocorticoid-resistance-is-reverted-by-lck-inhibition-in-pediatric-t-cell-acute-lymphoblastic-leukemia
#10
Valentina Serafin, Giorgia Capuzzo, Gloria Milani, Sonia Anna Minuzzo, Marica Pinazza, Roberta Bortolozzi, Silvia Bresolin, Elena Porcù, Chiara Frasson, Stefano Indraccolo, Giuseppe Basso, Benedetta Accordi
Pediatric T-acute lymphoblastic leukemia (T-ALL) patients often display resistance to glucocorticoid (GC) treatment. These patients, classified as Prednisone Poor Responders (PPR), have poorer outcome compared to the other pediatric T-ALL patients receiving a high-risk adapted therapy. Since glucocorticoids are administered to ALL patients during all the different phases of therapy, GC resistance represents an important challenge to be addressed in order to improve the outcome for these patients. Mechanisms underlying resistance are not yet fully unraveled, thus our research focused on the identification of deregulated signaling pathways to point out new targeted approaches...
November 3, 2017: Blood
https://www.readbyqxmd.com/read/29101163/cdk4-6-inhibition-augments-anti-tumor-immunity-by-enhancing-t-cell-activation
#11
Jiehui Deng, Eric S Wang, Russell W Jenkins, Shuai Li, Ruben Dries, Kathleen Yates, Sandeep Chhabra, Wei Huang, Hongye Liu, Amir R Aref, Elena Ivanova, Cloud Peter Paweletz, Michaela Bowden, Chensheng W Zhou, Grit S Herter-Sprie, Jessica A Sorrentino, John E Bisi, Patrick H Lizotte, Ashley A Merlino, Max M Quinn, Lauren E Bufe, Annan Yang, Yanxi Zhang, Hua Zhang, Peng Gao, Ting Chen, Megan E Cavanaugh, Amanda J Rode, Eric Haines, Patrick J Roberts, Jay C Strum, William G Richards, Jochen H Lorch, Sareh Parangi, Viswanath Gunda, Genevieve M Boland, Raphael Bueno, Sangeetha Palakurthi, Gordon J Freeman, Jerome Ritz, W Nicholas Haining, Norman E Sharpless, Haribabu Arthanari, Geoffrey I Shapiro, David A Barbie, Nathanael S Gray, Kwok-Kin Wong
Immune checkpoint blockade, exemplified by antibodies targeting the programmed death-1 (PD-1) receptor, can induce durable tumor regressions in some patients. To enhance the efficacy of existing immunotherapies, we screened for small molecules capable of increasing the activity of T cells suppressed by PD-1. Here, we show that short-term exposure to small molecule inhibitors of cyclin-dependent kinases 4 and 6 (CDK4/6) significantly enhances T cell activation, contributing to anti-tumor effects in vivo, due in part to de-repression of Nuclear Factor of Activated T cell (NFAT) family proteins and their target genes, critical regulators of T cell function...
November 3, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/29094385/the-neuronal-and-endocrine-roles-of-rcan1-in-health-and-disease
#12
Heshan Peiris, Damien J Keating
Regulator of calcineurin 1 (RCAN1) was first discovered as a gene located on human chromosome 21, expressed in neurons and overexpressed in the brains of Down Syndrome individuals. Increased expression of RCAN1 has been linked with not only Down Syndrome-associated pathology but also an associated neurological disorder, Alzheimer's Disease, in which neuronal RCAN1 expression is also increased. RCAN1 has additionally been demonstrated to effect other cell types including endocrine cells, with links to the pathogenesis of β-cell dysfunction in type 2 diabetes...
November 1, 2017: Clinical and Experimental Pharmacology & Physiology
https://www.readbyqxmd.com/read/29080087/the-role-of-the-endoplasmic-reticulum-protein-calreticulin-in-mediating-tgf-%C3%AE-stimulated-extracellular-matrix-production-in-fibrotic-disease
#13
REVIEW
Benjamin Y Owusu, Kurt A Zimmerman, Joanne E Murphy-Ullrich
Endoplasmic reticulum (ER) stress is a key factor contributing to fibrotic disease. Although ER stress is a short-term adaptive response, with chronic stimulation, it can activate pathways leading to fibrosis. ER stress can induce TGF-β signaling, a central driver of extracellular matrix production in fibrosis. This review will discuss the role of an ER protein, calreticulin (CRT), which has both chaperone and calcium regulatory functions, in fibrosis. CRT expression is upregulated in multiple different fibrotic diseases...
October 28, 2017: Journal of Cell Communication and Signaling
https://www.readbyqxmd.com/read/29077654/improved-pulse-wave-velocity-and-renal-function-in-individualized-calcineurin-inhibitor-treatment-by-immunomonitoring-the-randomized-controlled-calcineurin-inhibitor-sparing-cis-trial
#14
Claudia Sommerer, Janina Brocke, Thomas Bruckner, Matthias Schaier, Christian Morath, Stefan Meuer, Martin Zeier, Thomas Giese
BACKGROUND: A new immune monitoring tool which assesses the expression of nuclear factor of activated T-cells (NFAT)-regulated genes measures the functional effects of cyclosporine A. This is the first prospective randomized controlled study to compare standard pharmacokinetic monitoring by cyclosporine trough levels to NFAT-regulated gene expression (NFAT-RE). METHODS: Expression of the NFAT-regulated genes was determined by qRT-PCR at cyclosporine trough and peak level...
October 26, 2017: Transplantation
https://www.readbyqxmd.com/read/29077269/identification-of-a-potent-mar-element-from-the-human-genome-and-assessment-of-its-activity-in-stably-transfected-cho-cells
#15
Zheng-Wei Tian, Dan-Hua Xu, Tian-Yun Wang, Xiao-Yin Wang, Hong-Yan Xu, Chun-Peng Zhao, Guang-Hua Xu
Low-level and unstable transgene expression are common issues using the CHO cell expression system. Matrix attachment regions (MARs) enhance transgene expression levels, but additional research is needed to improve their function and to determine their mechanism of action. MAR-6 from CHO chromosomes actively mediates high and consistent gene expression. In this study, we compared the effects of two new MARs and MAR-6 on transgene expression in recombinant CHO cells and found one potent MAR element that can significantly increase transgene expression...
October 27, 2017: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/29073235/src-family-kinases-negatively-regulate-nfat-signaling-in-resting-human-t-cells
#16
Alan Baer, Winston Colon-Moran, Jinhua Xiang, Jack T Stapleton, Nirjal Bhattarai
T cell signaling is required for activation of both natural and therapeutic T cells including chimeric antigen receptor (CAR) T cells. Identification of novel factors and pathways regulating T cell signaling may aid in development of effective T cell therapies. In resting human T cells, the majority of Src-family of tyrosine kinases (SFKs) are inactive due to phosphorylation of a conserved carboxy-terminal tyrosine residue. Recently, a pool of enzymatically active SFKs has been identified in resting T cells; however, the significance of these is incompletely understood...
2017: PloS One
https://www.readbyqxmd.com/read/29058425/sophoridine-from-sophora-flower-attenuates-ovariectomy-induced-osteoporosis-through-the-rankl-erk-nfat-pathway
#17
Xiaoying Zhao, Lijuan Mei, Jinjin Pei, Zenggen Liu, Yun Shao, Yanduo Tao, Xiaoling Zhang, Lei Jiang
An imbalance in osteogenesis and osteoclastogenesis is a crucial pathological factor in the development of osteoporosis. Osteoclasts (OCs) play a pivotal role in osteoporosis, whose new therapy exploration has been focused on the suppression of OC formation. Sophoridine is found from the Chinese traditional food sophora flower to exhibit anti-osteoporosis capacity by screening. This study is focused on its anti-osteoporosis mechanism evaluation. The anti-osteoporosis effect of sophoridine, (15 mg kg(-1) body), was evaluated in ovariectomized (OVX) mice by monitoring changes in bone histomorphometry index, formation of osteoclasts from blood-derived mononuclear cells, and changes in the synthesis of pro-osteoclastogenic cytokines...
October 31, 2017: Journal of Agricultural and Food Chemistry
https://www.readbyqxmd.com/read/29054759/creld1-gene-variants-and-atrioventricular-septal-defects-in-down-syndrome
#18
Ambreen Asim, Sarita Agarwal, Inusha Panigrahi, Aditya Narayan Sarangi, Srinivasan Muthuswamy, Aditya Kapoor
Congenital heart defects (CHD) are seen in around 40% of the Down syndrome patients. Atrioventricular Septal Defect (AVSD) or endocardial cushion defect is commonest form of CHD in these children. CRELD1 gene is implicated in causation of sporadic AVSD. In the present study, we evaluated the association and significance of CRELD1 variants with AVSD in Down syndrome (DS) patients. Sequencing was done in blood samples from 3 groups: group I (DS with AVSD), group II (DS without AVSD) and group III (non-syndromic AVSD cases)...
October 17, 2017: Gene
https://www.readbyqxmd.com/read/29053621/isoproterenol-increases-rankl-expression-in-a-atf4-nfatc1-dependent-manner-in-mouse-osteoblastic-cells
#19
Kyunghwa Baek, Hyun-Jung Park, Jeong-Hwa Baek, Hyung-Ryong Kim
Sympathetic nervous system stimulation-induced β-adrenergic signal transduction is known to induce bone loss and increase of osteoclast activity. Although isoproterenol, a nonspecific β-adrenergic receptor agonist, has been shown to increase receptor activator of NF-κB ligand (RANKL), the details of the regulatory mechanisms remain unclear. In the present study, we investigated the role of the nuclear factor of activated T-cells (NFAT) in isoproterenol-induced RANKL expression in C2C12 and in primary cultured mouse calvarial cells...
October 20, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29038896/inducible-atf3-nfat-axis-aggravates-podocyte-injury
#20
Hong Zhang, Shun Liang, Yue Du, Ruizhao Li, Chaosheng He, Wenjian Wang, Shuangxin Liu, Zhiming Ye, Xinling Liang, Wei Shi, Bin Zhang
Podocyte injury and loss contribute to proteinuria, glomerulosclerosis, and eventually kidney failure. Activating transcription factor 3 (ATF3) is a stress inducible transcription factor that is transiently expressed following stimulation. However, we show for the first time an induction of ATF3 in podocytes from patients with chronic kidney disease, including minimal change disease, focal segmental glomerulosclerosis, and diabetic nephropathy. The role of ATF3 induction in podocytes under chronic conditions is currently unknown...
October 16, 2017: Journal of Molecular Medicine: Official Organ of the "Gesellschaft Deutscher Naturforscher und Ärzte"
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