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https://www.readbyqxmd.com/read/27919962/ascorbyl-stearate-promotes-apoptosis-through-intrinsic-mitochondrial-pathway-in-hela-cancer-cells
#1
Shirish D Mane, Maikho Thoh, Deepak Sharma, Santosh K Sandur, K Akhilender Naidu
BACKGROUND: Ascorbic acid is proposed to have antitumor potential against certain cancer types but has the limitation of requiring high doses for treating cancer. Ascorbyl stearate (ASC-S) is a fatty acid ester derivative of ascorbic acid with comparable potent apoptotic activity. The present study was aimed at understanding the pathway involved in apoptotic activity of ASC-S in cervical cancer cells. MATERIALS AND METHODS: The effect of ASC-S on reactive oxygen species (ROS), and mitochondrial membrane potential (MMP) was studied in HeLa cells...
December 2016: Anticancer Research
https://www.readbyqxmd.com/read/27910098/gata-3-specific-dnazyme-a-novel-approach-for-stratified-asthma-therapy
#2
REVIEW
Holger Garn, Harald Renz
It is now well established that type-2 immune mechanisms drive the inflammation in about 50% of asthma patients. The major cellular and molecular players regulating this important network have been identified. In terms of therapeutic intervention, cytokine and cytokine-receptor pathways have been given major attention, since these molecules are relatively easily accessible for a blockade through monoclonal antibodies, and a number of positive clinical results support this concept. However, targeting events controlling the type-2 immunity network upstream of selective cytokine pathways would be equally attractive...
December 2, 2016: European Journal of Immunology
https://www.readbyqxmd.com/read/27907007/exploring-regulatory-mechanisms-of-atrial-myocyte-hypertrophy-of-mitral-regurgitation-through-gene-expression-profiling-analysis-role-of-nfat-in-cardiac-hypertrophy
#3
Tzu-Hao Chang, Mien-Cheng Chen, Jen-Ping Chang, Hsien-Da Huang, Wan-Chun Ho, Yu-Sheng Lin, Kuo-Li Pan, Yao-Kuang Huang, Wen-Hao Liu, Chia-Chen Wu
BACKGROUND: Left atrial enlargement in mitral regurgitation (MR) predicts a poor prognosis. The regulatory mechanisms of atrial myocyte hypertrophy of MR patients remain unknown. METHODS AND RESULTS: This study comprised 14 patients with MR, 7 patients with aortic valve disease (AVD), and 6 purchased samples from normal subjects (NC). We used microarrays, enrichment analysis and quantitative RT-PCR to study the gene expression profiles in the left atria. Microarray results showed that 112 genes were differentially up-regulated and 132 genes were differentially down-regulated in the left atria between MR patients and NC...
2016: PloS One
https://www.readbyqxmd.com/read/27897008/tracing-co-regulatory-network-dynamics-in-noisy-single-cell-transcriptome-trajectories
#4
Pablo Cordero, Joshua M Stuart
The availability of gene expression data at the single cell level makes it possible to probe the molecular underpinnings of complex biological processes such as differentiation and oncogenesis. Promising new methods have emerged for reconstructing a progression 'trajectory' from static single-cell transcriptome measurements. However, it remains unclear how to adequately model the appreciable level of noise in these data to elucidate gene regulatory network rewiring. Here, we present a framework called Single Cell Inference of MorphIng Trajectories and their Associated Regulation (SCIMITAR) that infers progressions from static single-cell transcriptomes by employing a continuous parametrization of Gaussian mixtures in high-dimensional curves...
2016: Pacific Symposium on Biocomputing
https://www.readbyqxmd.com/read/27895176/the-syk-nfat-il-2-pathway-in-dendritic-cells-is-required-for-optimal-sterile-immunity-elicited-by-alum-adjuvants
#5
Hanif Javanmard Khameneh, Adrian W S Ho, Roberto Spreafico, Heidi Derks, Hazel Q Y Quek, Alessandra Mortellaro
Despite a long history and extensive usage of insoluble aluminum salts (alum) as vaccine adjuvants, the molecular mechanisms underpinning Ag-specific immunity upon vaccination remain unclear. Dendritic cells (DCs) are crucial initiators of immune responses, but little is known about the molecular pathways used by DCs to sense alum and, in turn, activate T and B cells. In this article, we show that alum adjuvanticity requires IL-2 specifically released by DCs, even when T cell secretion of IL-2 is intact. We demonstrate that alum, as well as other sterile particulates, such as uric acid crystals, induces DCs to produce IL-2 following initiation of actin-mediated phagocytosis that leads to Src and Syk kinase activation, Ca(2+) mobilization, and calcineurin-dependent activation of NFAT, the master transcription factor regulating IL-2 expression...
November 28, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/27893767/t-cells-of-infants-are-mature-but-hyporeactive-due-to-limited-ca2-influx
#6
Kristin Schmiedeberg, Hardy Krause, Friedrich-Wilhelm Röhl, Roland Hartig, Gerhard Jorch, Monika C Brunner-Weinzierl
CD4 T cells in human infants and adults differ in the initiation and strength of their responses. The molecular basis for these differences is not yet understood. To address this the principle key molecular events of TCR- and CD28-induced signaling in naive CD4 T cells, such as Ca2+ influx, NFAT expression, phosphorylation and translocation into the nucleus, ERK activation and IL-2 response, were analyzed over at least the first 3 years of life. We report dramatically reduced IL-2 and TNFα responses in naive CD31+ T cells during infancy...
2016: PloS One
https://www.readbyqxmd.com/read/27893713/phosphorylation-of-nfat3-by-cdk3-induces-cell-transformation-and-promotes-tumor-growth-in-skin-cancer
#7
T Xiao, J J Zhu, S Huang, C Peng, S He, J Du, R Hong, X Chen, A M Bode, W Jiang, Z Dong, D Zheng
The nuclear factor of activated T cells (NFAT) family proteins are transcription factors that regulate the expression of pro-inflammatory cytokines and other genes during the immune response. Although the NFAT proteins have been extensively investigated in the immune system, their role in cancer progression remains controversial. Here, we report that NFAT3 is highly expressed in various skin cancer cell lines and tumor tissues. Knockdown of endogenous NFAT3 expression by short hairpin RNA (shRNA) significantly inhibited tumor cell proliferation, colony formation and anchorage-independent cell growth...
November 28, 2016: Oncogene
https://www.readbyqxmd.com/read/27871461/nuclear-factor-of-activated-t-cells-nfat-regulates-soluble-fms-like-tyrosine-kinase-1-secretion-sflt-1-from-human-placenta
#8
Louie Ye, Amy Gratton, Natalie J Hannan, Ping Cannon, Minh Deo, Kirsten R Palmer, Stephen Tong, Tu'uhevaha J Kaitu'u-Lino, Fiona C Brownfoot
INTRODUCTION: Preeclampsia is a serious complication affecting 5-8% of pregnancies. Central to its pathogenesis is placental hypoxia and inflammation which leads to secretion of soluble fms-like tyrosine kinase 1 (sFlt-1). sFlt-1 causes widespread endothelial dysfunction. The molecular mechanisms regulating sFlt-1 production remain poorly understood. Recently, a binding site for the nuclear factor activated T cells (NFAT) transcription factor has been found on fms-like tyrosine kinase 1 (FLT-1) promoter...
December 2016: Placenta
https://www.readbyqxmd.com/read/27870307/abrogation-of-gap-junctional-communication-in-es-cells-results-in-a-disruption-of-primitive-endoderm-formation-in-embryoid-bodies
#9
Philipp Wörsdörfer, Felicitas Bosen, Martina Gebhardt, Nicole Russ, Katrin Zimmermann, David Komla Kessie, Thileepan Sekaran, Angela Egert, Süleyman Ergün, Hubert Schorle, Alexander Pfeifer, Frank Edenhofer, Klaus Willecke
Gap junctional intercellular communication (GJIC) has been suggested to be involved in early embryonic development but the actual functional role remained elusive. Connexin (Cx) 43 and Cx45 are co-expressed in embryonic stem (ES) cells, form gap junctions and are considered to exhibit adhesive function and/or to contribute to the establishment of defined communication compartments. Here we describe the generation of Cx43/Cx45-double deficient mouse ES cells to achieve almost complete breakdown of GJIC. Cre-loxP induced deletion of both, Cx43 and Cx45, results in a block of differentiation in embryoid bodies without affecting pluripotency marker expression and proliferation in ES cells...
November 21, 2016: Stem Cells
https://www.readbyqxmd.com/read/27865873/signaling-via-g-proteins-mediates-tumorigenic-effects-of-gpr87
#10
Kristine Niss Arfelt, Suzan Fares, Alexander H Sparre-Ulrich, Gertrud M Hjortø, Lærke S Gasbjerg, Ann-Sofie Mølleskov-Jensen, Tau Benned-Jensen, Mette M Rosenkilde
G protein-coupled receptors (GPCRs) constitute a large protein family of seven transmembrane (7TM) spanning proteins that regulate multiple physiological functions. GPR87 is overexpressed in several cancers and plays a role in tumor cell survival. Here, the basal activity of GPR87 was investigated in transiently transfected HEK293 cells, revealing ligand-independent coupling to Gαi, Gαq and Gα12/13. Furthermore, GPR87 showed a ligand-independent G protein-dependent activation of the downstream transcription factors CREB, NFκB, NFAT and SRE...
November 16, 2016: Cellular Signalling
https://www.readbyqxmd.com/read/27863227/control-of-nfat-isoform-activation-and-nfat-dependent-gene-expression-through-two-coincident-and-spatially-segregated-intracellular-ca-2-signals
#11
Pulak Kar, Gary R Mirams, Helen C Christian, Anant B Parekh
Excitation-transcription coupling, linking stimulation at the cell surface to changes in nuclear gene expression, is conserved throughout eukaryotes. How closely related coexpressed transcription factors are differentially activated remains unclear. Here, we show that two Ca(2+)-dependent transcription factor isoforms, NFAT1 and NFAT4, require distinct sub-cellular InsP3 and Ca(2+) signals for physiologically sustained activation. NFAT1 is stimulated by sub-plasmalemmal Ca(2+) microdomains, whereas NFAT4 additionally requires Ca(2+) mobilization from the inner nuclear envelope by nuclear InsP3 receptors...
November 17, 2016: Molecular Cell
https://www.readbyqxmd.com/read/27858144/th9-and-other-il-9-producing-cells-in-allergic-asthma
#12
REVIEW
Sonja Koch, Nina Sopel, Susetta Finotto
Allergic asthma is a worldwide increasing chronic disease of the airways which affects more than 300 million people. It is associated with increased IgE, mast cell activation, airway hyperresponsiveness (AHR), mucus overproduction and remodeling of the airways. Previously, this pathological trait has been associated with T helper type 2 (Th2) cells. Recently, different CD4(+) T cell subsets (Th17, Th9) as well as cells of innate immunity, like mast cells and innate lymphoid cells type 2 (ILC2s), which are all capable of producing the rediscovered cytokine IL-9, are known to contribute to this disease...
November 17, 2016: Seminars in Immunopathology
https://www.readbyqxmd.com/read/27849171/the-nuclear-receptor-ahr-controls-bone-homeostasis-by-regulating-osteoclast-differentiation-via-the-rank-c-fos-signaling-axis
#13
Takashi Izawa, Rieko Arakaki, Hiroki Mori, Takaaki Tsunematsu, Yasusei Kudo, Eiji Tanaka, Naozumi Ishimaru
The aryl hydrocarbon receptor (AhR) pathway plays a key role in receptor activator of NF-κB ligand (RANKL)-mediated osteoclastogenesis. However, the mechanism underlying the regulation of AhR expression in osteoclasts and the signaling pathway through which AhR controls osteoclastogenesis remain unclear. We found that the expression of AhR in bone marrow-derived osteoclasts was upregulated by RANKL at an earlier stage than was the expression of signature osteoclast genes such as those encoding cathepsin K and NFAT, cytoplasmic, calcineurin-dependent 1...
December 15, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/27833920/mir-20b-inhibits-t-cell-proliferation-and-activation-via-nfat-signaling-pathway-in-thymoma-associated-myasthenia-gravis
#14
Yanzhong Xin, Hongfei Cai, Tianyu Lu, Yan Zhang, Yue Yang, Youbin Cui
Purpose. We examined the role of miR-20b in development of thymoma-associated myasthenia gravis, especially in T cell proliferation and activation. Materials and Methods. Using qRT-PCR, we assessed expression levels of miR-20b and its target genes in cultured cells and patient samples and examined the proliferation of cultured cells, using MTT cell proliferation assays and flow cytometry based cell cycle analysis. Activation of T cells was determined by both flow cytometry and qRT-PCR of activation-specific marker genes...
2016: BioMed Research International
https://www.readbyqxmd.com/read/27829167/atf3-modulates-calcium-signaling-in-osteoclast-differentiation-and-activity-by-associating-with-c-fos-and-nfatc1-proteins
#15
Byung-Chul Jeong, Jung Ha Kim, Kabsun Kim, Inyoung Kim, Semun Seong, Nacksung Kim
Activating transcription factor 3 (ATF3), a member of the ATF/cAMP response element-binding protein family of transcription factors, has been implicated in the regulation of cell proliferation and differentiation. However, whether ATF3 is involved in osteoclast differentiation and activity has not been well-studied. In the present study, we examined the role of ATF3 in osteoclast differentiation and function. ATF3 expression was down-regulated during RANKL-induced osteoclast differentiation. Overexpression of ATF3 in bone marrow-derived monocyte/macrophage lineage cells (BMMs) promoted osteoclast differentiation and activity and strongly induced the expression of osteoclast genes encoding nuclear factor of activated T-cells c1 (NFATc1) and tartrate-resistant acid phosphatase (TRAP) compared to that in the control group...
November 6, 2016: Bone
https://www.readbyqxmd.com/read/27815505/transcription-factor-ets-2-acts-as-a-pre-induction-repressor-of-interleukin-2-il-2-transcription-in-naive-t-helper-lymphocytes
#16
Ioannis Panagoulias, Tassos Georgakopoulos, Ioanna Aggeletopoulou, Marios Agelopoulos, Dimitris Thanos, Athanasia Mouzaki
IL-2 is the first cytokine produced when naive T helper (Th) cells are activated and differentiate into dividing pre-Th0 proliferating precursors. IL-2 expression is blocked in naive, but not activated or memory Th cells, by the transcription factor Ets-2 that binds to the ARRE-2 element of the proximal IL-2 promoter. Ets-2 acts as an independent pre-induction repressor in naive Th cells and does not interact physically with the transcription factor NFAT that binds to the ARRE-2 element in activated Th cells...
November 3, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27813153/traf6-mediates-suppression-of-osteoclastogenesis-and-prevention-of-ovariectomy-induced-bone-loss-by-a-novel-prenylflavonoid
#17
E M Tan, L Li, I R Indran, N Chew, E L Yong
Given the limitations of current therapeutic options for postmenopausal osteoporosis, there is a need for alternatives with minimal adverse effects. In this study, we evaluated the effects of icaritin (ICT), a natural prenylflavonoid, on osteoclastogenesis both in vitro and in an ovariectomized (OVX)-rat model, and investigated its underlying molecular mechanism(s) of action. ICT inhibited osteoclast formation in two osteoclast precursor models, RAW 264.7 mouse monocyte cell line and human PBMC. ICT also inhibited sealing zone and resorption pit formation in a dose-dependent manner...
November 4, 2016: Journal of Bone and Mineral Research: the Official Journal of the American Society for Bone and Mineral Research
https://www.readbyqxmd.com/read/27789216/artesunate-suppresses-rankl-induced-osteoclastogenesis-through-inhibition-of-plc%C3%AE-1-ca-2-nfatc1-signaling-pathway-and-prevents-ovariectomy-induced-bone-loss
#18
Xiangzhou Zeng, Yueyang Zhang, Song Wang, Keng Wang, Lei Tao, Min Zou, Nana Chen, Jiake Xu, Shuwen Liu, Xiaojuan Li
Bone lytic diseases including osteoporosis, rheumatoid arthritis, and bone metastatic tumors affect hundreds of millions people worldwide. Targeting over-activated osteoclasts as an anti-resorptive treatment becomes an important strategy to treat osteolytic diseases. Artesunate is a compound derived from artemisinin (qinghaosu) and has been used to treat malaria and rheumatoid arthritis clinically in China, but its role in osteolysis is unknown. Here, we found that artesunate could suppress RANKL-induced osteoclastogenesis and bone resorption from 1...
October 24, 2016: Biochemical Pharmacology
https://www.readbyqxmd.com/read/27787949/pasireotide-prevents-nuclear-factor-of-activated-t-cells-nuclear-translocation-and-acts-as-a-protective-agent-in-aminoglycoside-induced-auditory-hair-cell-loss
#19
Daniel Bodmer, Adrijana Perkovic, Marijana Sekulic-Jablanovic, Matthew B Wright, Vesna Petkovic
Hearing impairment is a global health problem with a high socioeconomic impact. Damage to auditory hair cells (HCs) in the inner ear as a result of aging, disease, trauma, or toxicity, underlies the majority of cases of sensorineural hearing loss. Previously we demonstrated that the Ca(2+) -sensitive neuropeptide, somatostatin (SST), and an analog, octreotide, protect HCs from gentamicin-induced cell death in vitro. Aminoglycosides such as gentamicin trigger a calcium ion influx (Ca(2+) ) that activates pro-apoptotic signaling cascades in HCs...
October 27, 2016: Journal of Neurochemistry
https://www.readbyqxmd.com/read/27778276/transcriptional-modulation-of-regulatory-t-cell-development-by-novel-regulators-nr4as
#20
Hee Yeon Won, Eun Sook Hwang
Regulatory T (Treg) cells with high expression of both CD25 and Foxp3 are developed in the thymus and also peripheral tissues. Treg cells suppress the activation and functions of effector T cells raised against specific antigens and are crucial for maintaining immune homeostasis. Treg cell development is associated with the induction of and epigenetic alterations of forkhead transcription factor Foxp3. Foxp3 expression is increased by the activation of several transcription factors including nuclear factor-kappa B (NF-κB), nuclear factor of activated T cells (NFAT), and Smad3 in response to various signals such as TGFβ, retinoic acid, and rapamycin...
October 25, 2016: Archives of Pharmacal Research
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