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https://www.readbyqxmd.com/read/29723850/the-favored-mechanism-for-coping-with-acute-cold-stress-upregulation-of-mir-210-in-rats
#1
Wenjin Guo, Shuai Lian, Li Zhen, Shucheng Zang, Yan Chen, Limin Lang, Bin Xu, Jingru Guo, Hong Ji, Jianfa Wang, Shoupeng Fu, Liping Zhang, Huanmin Yang
BACKGROUND/AIMS: The main aim of this study was to determine the mechanisms by which rno-miR-210-3p affects changes in gene expression, metabolism, apoptosis and proliferation of cells under acute cold stress (ACS) conditions. METHODS: The treatment group (n=6, weight 340±20 g) was exposed to ACS (temperature 4±0.5°C, relative humidity 45±0.5%) and the control group (n=6, weight 340±20 g) to normal temperature (NT) (temperature 24±0.5°C, relative humidity 45±0...
April 28, 2018: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29705335/molecular-mechanisms-of-platelet-activation-and-aggregation-induced-by-breast-cancer-cells
#2
Marta Zarà, Ilaria Canobbio, Caterina Visconte, Jessica Canino, Mauro Torti, Gianni Francesco Guidetti
Tumor cell-induced platelet aggregation represents a critical process both for successful metastatic spread of the tumor and for the development of thrombotic complications in cancer patients. To get further insights into this process, we investigated and compared the molecular mechanisms of platelet aggregation induced by two different breast cancer cell lines (MDA-MB-231 and MCF7) and a colorectal cancer cell line (Caco-2). All the three types of cancer cells were able to induce comparable platelet aggregation, which, however, was observed exclusively in the presence of CaCl2 and autologous plasma...
April 26, 2018: Cellular Signalling
https://www.readbyqxmd.com/read/29622678/calcium-induced-structural-rearrangements-release-autoinhibition-in-the-rap-gef-caldag-gefi
#3
Aaron A Cook, Wei Deng, Jinqi Ren, Renhao Li, John Sondek, Wolfgang Bergmeier
Platelets are recruited to sites of vascular injury where they are activated and aggregate to form a hemostatic plug. This process requires the activation of the small GTPase Rap1B by its cognate guanine nucleotide exchange factor CalDAG-GEFI. Studies on platelet function suggest that CalDAG-GEFI activity is regulated by changes in cytosolic calcium, but the exact molecular mechanism is poorly understood. Here, we show that purified CalDAG-GEFI is autoinhibited and directly regulated by calcium. Substitutions of putative calcium-binding residues within the canonical EF hands of CalDAG-GEFI diminish its capacity to activate Rap1B...
April 5, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29599749/mir-518b-enhances-human-trophoblast-cell-proliferation-through-targeting-rap1b-and-activating-ras-mapk-signal
#4
Ming Liu, Yongqing Wang, Huifen Lu, Hao Wang, Xiaoming Shi, Xuan Shao, Yu-Xia Li, Yangyu Zhao, Yan-Ling Wang
Preeclampsia is a pregnancy-specific complication defined as newly onset gestational hypertension and proteinuria. Deficiency in placental development is considered as the predominant cause of preeclampsia. Our previous study found that the expression of miR-518b increased significantly in the preeclamptic placentas, indicating the potential participation of this small RNA in the occurrence of preeclampsia. In this study, data analysis using multiple databases predicted Rap1b as a candidate target of miR-518b...
2018: Frontiers in Endocrinology
https://www.readbyqxmd.com/read/29559227/rap1b-enhances-the-invasion-and-migration-of-hepatocellular-carcinoma-cells-by-up-regulating-twist-1
#5
Zhenrong Tang, Hong Peng, Juan Chen, Yuyang Liu, Shaoying Yan, Gangfeng Yu, Qiuxu Chen, Hua Tang, Shengchun Liu
Rap1b was found be dysregulated in several types of cancers. Previously, we have demonstrated that Rap1b affects proliferation, migration and invasion of hepatocellular carcinoma (HCC) cells. However, the definite function of Rap1b in HCC remains unknown. Here, we reported that Rap1b was significantly up-regulated in HCC tissues compared with the non-tumoral liver tissues. Overexpression of Rap1b promoted tumor growth and migration in vitro and tumor formation in vivo. Oppositely, inhibition of Rap1b suppressed the proliferation and migration of HCC cells...
March 17, 2018: Experimental Cell Research
https://www.readbyqxmd.com/read/29222111/rap1b-promotes-vegf-induced-endothelial-permeability-and-is-required-for-dynamic-regulation-of-the-endothelial-barrier
#6
Sribalaji Lakshmikanthan, Magdalena Sobczak, Sergio Li Calzi, Lynn Shaw, Maria B Grant, Magdalena Chrzanowska-Wodnicka
Vascular endothelial growth factor (VEGF), a key angiogenic and permeability factor, plays an important role in new blood vessel formation. However, abnormal VEGF-induced VEGFR2 signaling leads to hyperpermeability. We have shown previously that Rap1, best known for promoting cell adhesion and vessel stability, is a critical regulator of VEGFR2-mediated angiogenic and shear-stress EC responses. To determine the role of Rap1 role in endothelial barrier dynamics, we examined vascular permeability in EC-specific Rap1A- and Rap1B-knockout mice, cell-cell junction remodeling and EC monolayer resistivity in Rap1-deficient ECs under basal, inflammatory or elevated VEGF conditions...
January 10, 2018: Journal of Cell Science
https://www.readbyqxmd.com/read/29170462/structure-of-rap1b-bound-to-talin-reveals-a-pathway-for-triggering-integrin-activation
#7
Liang Zhu, Jun Yang, Thomas Bromberger, Ashley Holly, Fan Lu, Huan Liu, Kevin Sun, Sarah Klapproth, Jamila Hirbawi, Tatiana V Byzova, Edward F Plow, Markus Moser, Jun Qin
Activation of transmembrane receptor integrin by talin is essential for inducing cell adhesion. However, the pathway that recruits talin to the membrane, which critically controls talin's action, remains elusive. Membrane-anchored mammalian small GTPase Rap1 is known to bind talin-F0 domain but the binding was shown to be weak and thus hardly studied. Here we show structurally that talin-F0 binds to human Rap1b like canonical Rap1 effectors despite little sequence homology, and disruption of the binding strongly impairs integrin activation, cell adhesion, and cell spreading...
November 23, 2017: Nature Communications
https://www.readbyqxmd.com/read/29168172/extracellular-adenosine-induced-rac1-activation-in-pulmonary-endothelium-molecular-mechanisms-and-barrier-protective-role
#8
Anita Kovacs-Kasa, Kyung Mi Kim, Mary Cherian-Shaw, Stephen M Black, David J Fulton, Alexander D Verin
We have previously shown that Gs-coupled adenosine receptors (A2a) are primarily involved in adenosine-induced human pulmonary artery endothelial cell (HPAEC) barrier enhancement. However, the downstream events that mediate the strengthening of the endothelial cell (EC) barrier via adenosine signaling are largely unknown. In the current study, we tested the overall hypothesis that adenosine-induced Rac1 activation and EC barrier enhancement is mediated by Gs-dependent stimulation of cAMP-dependent Epac1-mediated signaling cascades...
August 2018: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/29158262/the-epac-rap1-pathway-prevents-and-reverses-cytokine-induced-retinal-vascular-permeability
#9
Carla J Ramos, Chengmao Lin, Xuwen Liu, David A Antonetti
Increased retinal vascular permeability contributes to macular edema, a leading cause of vision loss in eye pathologies such as diabetic retinopathy, age-related macular degeneration, and central retinal vein occlusions. Pathological changes in vascular permeability are driven by growth factors such as VEGF and pro-inflammatory cytokines such as TNF-α. Identifying the pro-barrier mechanisms that block vascular permeability and restore the blood-retinal barrier (BRB) may lead to new therapies. The cAMP-dependent guanine nucleotide exchange factor (EPAC) exchange-protein directly activated by cAMP promotes exchange of GTP in the small GTPase Rap1...
January 12, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29062863/the-vacuolar-h-atpase-v-0-subunit-d-2-is-associated-with-chondrocyte-hypertrophy-and-supports-chondrocyte-differentiation
#10
Babatunde A Ayodele, Michiko Mirams, Charles N Pagel, Eleanor J Mackie
Chondrocyte hypertrophy makes important contributions to bone development and growth. We have investigated a number of novel cartilage genes identified in a recent transcriptomic study to determine whether they are differentially expressed between different zones of equine foetal growth cartilage. Twelve genes ( ATP6V0D2 , BAK1 , DDX5 , GNB1 , PIP4K2A , RAP1B , RPS7 , SRSF3 , SUB1 , TMSB4 , TPI1 and WSB2 ) were found to be more highly expressed in the zone of hypertrophic chondrocytes than in the reserve or proliferative zones, whereas FOXA3 and SERPINA1 were expressed at lower levels in the hypertrophic zone than in the reserve zone...
December 2017: Bone Reports
https://www.readbyqxmd.com/read/28953373/identification-of-the-privileged-position-in-the-imidazo-1-2-a-pyridine-ring-of-phosphonocarboxylates-for-development-of-rab-geranylgeranyl-transferase-rggt-inhibitors
#11
Aleksandra Kaźmierczak, Damian Kusy, Sanna P Niinivehmas, Joanna Gmach, Łukasz Joachimiak, Olli T Pentikäinen, Edyta Gendaszewska-Darmach, Katarzyna M Błażewska
Members of the Rab GTPase family are master regulators of vesicle trafficking. When disregulated, they are associated with a number of pathological states. The inhibition of RGGT, an enzyme responsible for post-translational geranylgeranylation of Rab GTPases represents one way to control the activity of these proteins. Because the number of molecules modulating RGGT is limited, we combined molecular modeling with biological assays to ascertain how modifications of phosphonocarboxylates, the first reported RGGT inhibitors, rationally improve understanding of their structure-activity relationship...
November 9, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28952923/a-histidine-ph-sensor-regulates-activation-of-the-ras-specific-guanine-nucleotide-exchange-factor-rasgrp1
#12
Yvonne Vercoulen, Yasushi Kondo, Jeffrey S Iwig, Axel B Janssen, Katharine A White, Mojtaba Amini, Diane L Barber, John Kuriyan, Jeroen P Roose
RasGRPs are guanine nucleotide exchange factors that are specific for Ras or Rap, and are important regulators of cellular signaling. Aberrant expression or mutation of RasGRPs results in disease. An analysis of RasGRP1 SNP variants led to the conclusion that the charge of His 212 in RasGRP1 alters signaling activity and plasma membrane recruitment, indicating that His 212 is a pH sensor that alters the balance between the inactive and active forms of RasGRP1. To understand the structural basis for this effect we compared the structure of autoinhibited RasGRP1, determined previously, to those of active RasGRP4:H-Ras and RasGRP2:Rap1b complexes...
September 27, 2017: ELife
https://www.readbyqxmd.com/read/28924375/lncrna-afap1-as-functions-as-a-competing-endogenous-rna-to-regulate-rap1b-expression-by-sponging-mir-181a-in-the-hscr
#13
Guanglin Chen, Lei Peng, Zhongxian Zhu, Chunxia Du, Ziyang Shen, Rujin Zang, Yang Su, Yankai Xia, Weibing Tang
Background: Long noncoding RNAs (lncRNAs) have recently emerged as important regulators in a broad spectrum of cellular processes including development and disease. Despite the known engagement of the AFAP1-AS in several human diseases, its biological function in Hirschsprung disease (HSCR) remains elusive. Methods: We used qRT-PCR to detect the relative expression of AFAP1-AS in 64 HSCR bowel tissues and matched normal intestinal tissues. The effects of AFAP1-AS on cell proliferation, migration, cell cycle, apoptosis and cytoskeletal organization were evaluated using CCK-8, transwell assay, flow cytometer analysis and immunofluorescence, in 293T and SH-SY5Y cell lines, respectively...
2017: International Journal of Medical Sciences
https://www.readbyqxmd.com/read/28921447/structure-pharmacology-and-roles-in-physiology-of-the-p2y-12-receptor
#14
Ivar von Kügelgen
P2Y receptors are G-protein-coupled receptors (GPCRs) for extracellular nucleotides. The platelet ADP-receptor which has been denominated P2Y12 receptor is an important target in pharmacotherapy. The receptor couples to Gαi2 mediating an inhibition of cyclic AMP accumulation and additional downstream events including the activation of phosphatidylinositol-3-kinase and Rap1b proteins. The nucleoside analogue ticagrelor and active metabolites of the thienopyridine compounds ticlopidine, clopidogrel and prasugrel block P2Y12 receptors and, thereby, inhibit ADP-induced platelet aggregation...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28917843/rapgef2-a-guanine-nucleotide-exchange-factor-for-rap1-small-gtpases-plays-a-crucial-role-in-adherence-junction-aj-formation-in-radial-glial-cells-through-erk-mediated-upregulation-of-the-aj-constituent-protein-expression
#15
Maged Ibrahim Farag, Yoko Yoshikawa, Kazuhiro Maeta, Tohru Kataoka
Rapgef2 and Rapgef6 define a subfamily of guanine nucleotide exchange factors for Rap1, characterized by possession of the Ras/Rap-associating domains and implicated in the etiology of schizophrenia. We previously found that dorsal telencephalon-specific Rapgef2 conditional knockout mice exhibits severe defects in formation of apical surface adherence junctions (AJs) and localization of radial glial cells (RGCs). In this study, we analyze the underlying molecular mechanism by using primary cultures of RGCs established from the developing cerebral cortex...
November 4, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28591224/low-dose-glucocorticoids-suppresses-ovarian-tumor-growth-and-metastasis-in-an-immunocompetent-syngeneic-mouse-model
#16
Kai-Ti Lin, Shu-Pin Sun, Jui-I Wu, Lu-Hai Wang
Ovarian cancer has the highest mortality rate among gynecologic malignancies. Despite chemotherapy and surgical debulking options, ovarian cancer recurs and disseminates frequently with a poor prognosis. We previously reported a novel role of glucocorticoids (GCs) in metastatic ovarian cancer by upregulating microRNA-708. In this study, we used an immunocompetent syngeneic mouse model and further evaluated the effect and optimal dosages of GCs in treating metastatic ovarian cancer. The treatment of C57BL/6-derived ovarian cancer ID-8 cells with a synthetic GC, dexamethasone (DEX), induced the expression of microRNA-708, leading to decreased cell migration and invasion through targeting Rap1B...
2017: PloS One
https://www.readbyqxmd.com/read/28551849/long-non-coding-rna-malat1-promotes-proliferation-and-suppresses-apoptosis-of-glioma-cells-through-derepressing-rap1b-by-sponging-mir-101
#17
Zhenjiang Li, Chenyang Xu, Bingqian Ding, Ming Gao, Xinting Wei, Nan Ji
Long non-coding RNAs (lncRNAs) have been recently shown to be dysregulated and closely related to several cancers. Here, we aimed to elucidate the function and the possible molecular mechanisms of lncRNA Metastasis-associated lung Adenocarcinoma transcript-1 (MALAT1) in human glioma. Quantitative real-time PCR (qRT-PCR) was used to detect the expressions of MALAT1, miR-101 and Rap1B mRNA in U251 and U87 cells. The protein level of Rap1B was examined by western blot assays. Moreover, the proliferation and apoptosis of U251 and U87 cells were determined by CCK-8 assay and flow cytometry analysis, respectively...
August 2017: Journal of Neuro-oncology
https://www.readbyqxmd.com/read/28520221/rap1b-is-an-effector-of-axin2-regulating-crosstalk-of-signaling-pathways-during-skeletal-development
#18
Takamitsu Maruyama, Ming Jiang, Alycia Abbott, H-M Ivy Yu, Qirong Huang, Magdalena Chrzanowska-Wodnicka, Emily I Chen, Wei Hsu
Recent identification and isolation of suture stem cells capable of long-term self-renewal, clonal expanding, and differentiating demonstrate their essential role in calvarial bone development, homeostasis, and injury repair. These bona fide stem cells express a high level of Axin2 and are able to mediate bone regeneration and repair in a cell autonomous fashion. The importance of Axin2 is further demonstrated by its genetic inactivation in mice causing skeletal deformities resembling craniosynostosis in humans...
September 2017: Journal of Bone and Mineral Research: the Official Journal of the American Society for Bone and Mineral Research
https://www.readbyqxmd.com/read/28256057/interrupted-bipartite-clavicle-as-a-diagnostic-clue-in-kabuki-syndrome
#19
Maria Haanpää, Helena Schlecht, Gauri Batra, Jill Clayton-Smith, Sofia Douzgou
Kabuki syndrome is a rare developmental disorder characterized by typical facial features, postnatal growth deficiency, mild to moderate intellectual disability, and minor skeletal anomalies. It is caused by mutations of the KMT2D and KDM6A genes while recently RAP1A and RAP1B mutations have been shown to rarely contribute to the pathogenesis. We report two patients' presentation of Kabuki syndrome caused by different KMT2D mutations, both including an interrupted/bipartite clavicle. The clinical diagnosis of Kabuki syndrome may be challenging, especially in younger patients and we suggest that the observation of a bipartite clavicle may be an additional diagnostic clue to prompt investigation for Kabuki syndrome...
April 2017: American Journal of Medical Genetics. Part A
https://www.readbyqxmd.com/read/28148733/dynamic-interaction-and-phospho-proteomics-reveal-lck-as-a-major-signaling-hub-of-cd147-in-t-cells
#20
Verena Supper, Ingrid Hartl, Cyril Boulègue, Anna Ohradanova-Repic, Hannes Stockinger
Numerous publications have addressed CD147 as a tumor marker and regulator of cytoskeleton, cell growth, stress response, or immune cell function; however, the molecular functionality of CD147 remains incompletely understood. Using affinity purification, mass spectrometry, and phosphopeptide enrichment of isotope-labeled peptides, we examined the dynamic of the CD147 microenvironment and the CD147-dependent phosphoproteome in the Jurkat T cell line upon treatment with T cell stimulating agents. We identified novel dynamic interaction partners of CD147 such as CD45, CD47, GNAI2, Lck, RAP1B, and VAT1 and, furthermore, found 76 CD147-dependent phosphorylation sites on 57 proteins...
March 15, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
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