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https://www.readbyqxmd.com/read/28529061/benzo-a-pyrene-7-8-diol-9-10-epoxide-suppresses-the-migration-and-invasion-of-human-extravillous-trophoblast-htr-8-svneo-cells-by-down-regulating-mmp2-through-inhibition-of-fak-src-pi3k-akt-pathway
#1
Rong Wang, Weiping Wang, Lin Ao, Zhi Wang, Xianglin Hao, Huidong Zhang
Moderate invasion of trophoblasts into the endometrium is crucial for successful pregnancy. Benzo[a]pyrene-7,8-diol-9,10-epoxide (BPDE) is a carcinogenic metabolite of benzo[a]pyrene which causes various diseases. We investigated the effects of BPDE on migration and invasion of trophoblast HTR-8/SVneo cells. Migration and invasion of cells exposed to 0.25-1.0μM BPDE for 24h were significantly inhibited. Moreover, tube formation of human umbilical vein endothelial cell (HUVEC) was also significantly reduced after incubation with HTR-8/SVneo cells treated with 0...
May 18, 2017: Toxicology
https://www.readbyqxmd.com/read/28528309/maintenance-of-claudin-3-expression-and-the-barrier-functions-of-intercellular-junctions-in-parotid-acinar-cells-via-the-inhibition-of-src-signaling
#2
Megumi Yokoyama, Takanori Narita, Hajime Sakurai, Osamu Katsumata-Kato, Hiroshi Sugiya, Junko Fujita-Yoshigaki
OBJECTIVES: Salivary acinar and duct cells show different expression patterns of claudins, which may reflect their different functions. To study the role of claudins in saliva secretion, we examined alterations in the expression patterns of cell adhesion molecules in parotid glands of γ-irradiated rats and analyzed the influence of those changes on intercellular barrier function using primary cultures of parotid acinar cells. DESIGN: Rats were γ-irradiated with doses of 5, 15 or 20Gy, and expression levels of cell adhesion molecules were examined by immunoblotting analysis...
May 15, 2017: Archives of Oral Biology
https://www.readbyqxmd.com/read/28525838/design-synthesis-and-evaluation-of-azaacridine-derivatives-as-dual-target-egfr-and-src-kinase-inhibitors-for-antitumor-treatment
#3
Zhishan Cui, Shaopeng Chen, Yanwei Wang, Chunmei Gao, Yuzong Chen, Chunyan Tan, Yuyang Jiang
Overexpression of EGFR is often associated with advanced stage disease and poor prognosis. In certain cancers, Src works synergistically with EGFR to promote proliferation, survival, invasion and metastasis. Development of dual-target drugs against EGFR and Src is of therapeutic advantage against these cancers. Based on molecular docking and our previous studies, we rationally designed a new series of azaacridine derivatives as potent EGFR and Src dual inhibitors. Most of the synthesized azaacridines displayed good antiproliferative activity against K562 and A549 cells...
May 11, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28522963/the-f-actin-binding-protein-cortactin-regulates-the-dynamics-of-the-exocytotic-fusion-pore-through-its-sh3-domain
#4
Arlek M González-Jamett, María J Guerra, María J Olivares, Valentina Haro-Acuña, Ximena Baéz-Matus, Jacqueline Vásquez-Navarrete, Fanny Momboisse, Narcisa Martinez-Quiles, Ana M Cárdenas
Upon cell stimulation, the network of cortical actin filaments is rearranged to facilitate the neurosecretory process. This actin rearrangement includes both disruption of the preexisting actin network and de novo actin polymerization. However, the mechanism by which a Ca(2+) signal elicits the formation of new actin filaments remains uncertain. Cortactin, an actin-binding protein that promotes actin polymerization in synergy with the nucleation promoting factor N-WASP, could play a key role in this mechanism...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/28522807/traf3-enhances-tcr-signaling-by-regulating-the-inhibitors-csk-and-ptpn22
#5
Alicia M Wallis, Ellie C Wallace, Bruce S Hostager, Zuoan Yi, Jon C D Houtman, Gail A Bishop
The adaptor protein TNF receptor associated factor (TRAF) 3 is required for effective TCR signaling and normal T cell effector functions, and associates with the CD3/CD28 complex upon activation. To determine how TRAF3 promotes proximal TCR signaling, we studied TRAF3-deficient mouse and human T cells, which showed a marked reduction in activating phosphorylation of the TCR-associated kinase Lck. The impact of TRAF3 on this very early signaling event led to the hypothesis that TRAF3 restrains one or both of two known inhibitors of Lck, C-terminal Src kinase (Csk) and protein tyrosine phosphatase N22 (PTPN22)...
May 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28522592/sensitization-of-egfr-wild-type-non-small-cell-lung-cancer-cells-to-egfr-tyrosine-kinase-inhibitor-erlotinib
#6
Judith Raimbourg, Marie-Pierre Joalland, Mathilde Cabart, Ludmilla de Plater, Fanny Bouquet, Ariel Savina, Didier Decaudin, Jaafar Bennouna, François M Vallette, Lisenn Lalier
The benefit of EGFR-TKI in non-small cell lung cancer has been demonstrated in mutant EGFR tumors as first-line treatment but the benefit in wild-type EGFR tumors is marginal as well as restricted to maintenance therapy in pretreated patients. This work aimed at questioning the effects of cisplatin initial treatment on the EGFR pathway in non-small cell lung cancer and the functional consequences in vitro and in in vivo animal models of Patient-Derived Xenografts (PDX). We establish here that cisplatin pretreatment specifically sensitizes wild-type EGFR expressing cells to erlotinib, contrary to what happens in mutant-EGFR cells and with a blocking EGFR antibody, both in vitro and in vivo The sensitization entails the activation of the kinase Src upstream of EGFR, thereafter transactivating EGFR through a ligand-independent activation...
May 18, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28522571/flt3-and-flt3-itd-phosphorylate-and-inactivate-the-cyclin-dependent-kinase-inhibitor-p27kip1-in-acute-myeloid-leukemia
#7
Ines Peschel, Silvio R Podmirseg, Martin Taschler, Justus Duyster, Katharina S Götze, Heinz Sill, David Nachbaur, Heidelinde Jäkel, Ludger Hengst
p27Kip1 can prevent cell proliferation by inactivating cyclin-dependent kinases. This function is impaired upon phosphorylation of p27 at tyrosine residue 88. We observed that FLT3 and FLT3-ITD can directly bind and selectively phosphorylate p27 on this residue. Inhibition of FLT3-ITD in cell lines strongly reduced p27 tyrosine 88 phosphorylation and resulted in increased p27 levels and cell cycle arrest. Subsequent analysis revealed the presence of tyrosine 88 phosphorylated p27 in primary patient samples...
May 18, 2017: Haematologica
https://www.readbyqxmd.com/read/28520795/birc6-mediates-imatinib-resistance-independently-of-mcl-1
#8
Denis O Okumu, Michael P East, Merlin Levine, Laura E Herring, Raymond Zhang, Thomas S K Gilbert, David W Litchfield, Yanping Zhang, Lee M Graves
Baculoviral IAP repeat containing 6 (BIRC6) is a member of the inhibitors of apoptosis proteins (IAPs), a family of functionally and structurally related proteins that inhibit apoptosis. BIRC6 has been implicated in drug resistance in several different human cancers, however mechanisms regulating BIRC6 have not been extensively explored. Our phosphoproteomic analysis of an imatinib-resistant chronic myelogenous leukemia (CML) cell line (MYL-R) identified increased amounts of a BIRC6 peptide phosphorylated at S480, S482, and S486 compared to imatinib-sensitive CML cells (MYL)...
2017: PloS One
https://www.readbyqxmd.com/read/28516374/role-of-lps-elicited-signaling-in-triggering-gastric-mucosal-inflammatory-responses-to-h-pylori-modulatory-effect-of-ghrelin
#9
REVIEW
B L Slomiany, A Slomiany
Infection with Helicobacter pylori is a primary culprit in the etiology of gastric disease, and its cell-wall lipopolysaccharide (LPS) is recognized as a potent endotoxin responsible for triggering a pattern of the mucosal inflammatory responses. The engagement by the LPS of gastric mucosal Toll-like receptor 4 (TLR4) leads to initiation of signal transduction events characterized by the activation of mitogen-activated protein kinase (MAPK) cascade, induction of phosphoinositide-specific phospholipase C (PLC)/protein kinase C (PKC)/phosphatidylinositol 3-kinase (PI3K) pathway, and up-regulation in Src/Akt...
May 17, 2017: Inflammopharmacology
https://www.readbyqxmd.com/read/28514658/cns-macrophages-control-neurovascular-development-via-cd95l
#10
Si Chen, Nathalie Tisch, Marcel Kegel, Rosario Yerbes, Robert Hermann, Hannes Hudalla, Cecilia Zuliani, Gülce Sila Gülcüler, Klara Zwadlo, Jakob von Engelhardt, Carmen Ruiz de Almodóvar, Ana Martin-Villalba
The development of neurons and vessels shares striking anatomical and molecular features, and it is presumably orchestrated by an overlapping repertoire of extracellular signals. CNS macrophages have been implicated in various developmental functions, including the morphogenesis of neurons and vessels. However, whether CNS macrophages can coordinately influence neurovascular development and the identity of the signals involved therein is unclear. Here, we demonstrate that activity of the cell surface receptor CD95 regulates neuronal and vascular morphogenesis in the post-natal brain and retina...
May 16, 2017: Cell Reports
https://www.readbyqxmd.com/read/28512713/matairesinol-suppresses-neuroinflammation-and-migration-associated-with-src-and-erk1-2-nf-%C3%AE%C2%BAb-pathway-in-activating-bv2-microglia
#11
Peng Xu, Meng-Wei Huang, Chen-Xi Xiao, Fen Long, Ying Wang, Si-Yu Liu, Wan-Wan Jia, Wei-Jun Wu, Di Yang, Jin-Feng Hu, Xin-Hua Liu, Yi-Zhun Zhu
Chronic neuroinflammation is a pathological feature of neurodegenerative diseases. Inhibition of microglia-mediated neuroinflammation might be a potential strategy for neurodegeneration. Matairesinol, a dibenzylbutyrolactone plant lignan, presents in a wide variety of foodstuffs. It has been found to possess anti-angiogenic, anti-oxidative, anti-cancer and anti-fungal activities. In the present study, we investigated the anti-neuroinflammation effects of matairesinol on lipopolysaccharide (LPS)-induced BV2 microglia cells and the related molecular mechanisms...
May 17, 2017: Neurochemical Research
https://www.readbyqxmd.com/read/28512645/regulation-of-discrete-functional-responses-by-syk-and-src-family-tyrosine-kinases-in-human-neutrophils
#12
Thornin Ear, Olga Tatsiy, Frédérick L Allard, Patrick P McDonald
Neutrophils play a critical role in innate immunity and also influence adaptive immune responses. This occurs in good part through their production of inflammatory and immunomodulatory cytokines, in conjunction with their prolonged survival at inflamed foci. While a picture of the signaling machinery underlying these neutrophil responses is now emerging, much remains to be uncovered. In this study, we report that neutrophils constitutively express various Src family isoforms (STKs), as well as Syk, and that inhibition of these protein tyrosine kinases selectively hinders inflammatory cytokine generation by acting posttranscriptionally...
2017: Journal of Immunology Research
https://www.readbyqxmd.com/read/28508887/an-evolutionary-switch-in-nd2-enables-src-kinase-regulation-of-nmda-receptors
#13
David P Scanlon, Alaji Bah, Mickaël Krzeminski, Wenbo Zhang, Heather L Leduc-Pessah, Yi Na Dong, Julie D Forman-Kay, Michael W Salter
The non-receptor tyrosine kinase Src is a key signalling hub for upregulating the function of N-methyl D-aspartate receptors (NMDARs). Src is anchored within the NMDAR complex via NADH dehydrogenase subunit 2 (ND2), a mitochondrially encoded adaptor protein. The interacting regions between Src and ND2 have been broadly identified, but the interaction between ND2 and the NMDAR has remained elusive. Here we generate a homology model of ND2 and dock it onto the NMDAR via the transmembrane domain of GluN1. This interaction is enabled by the evolutionary loss of three helices in bilaterian ND2 proteins compared to their ancestral homologues...
May 16, 2017: Nature Communications
https://www.readbyqxmd.com/read/28508421/subversion-of-host-kinases-a-key-network-in-cellular-signaling-hijacked-by-helicobacter-pylori-caga
#14
REVIEW
Nicole Tegtmeyer, Matthias Neddermann, Carmen Isabell Asche, Steffen Backert
Helicobacter pylori is a paradigm of persistent pathogens and major risk factor for developing severe diseases including adenocarcinoma in the human stomach. An important bacterial factor linked to gastric disease progression is the cag pathogenicity island-encoded type-IV secretion system (T4SS) effector protein CagA. Translocated CagA undergoes tyrosine phosphorylation at EPIYA-motifs and then activates or inactivates multiple host signaling proteins in a phosphorylation-dependent and phosphorylation-independent fashion...
May 15, 2017: Molecular Microbiology
https://www.readbyqxmd.com/read/28506883/effects-of-cardiotonic-steroids-on-isolated-perfused-kidney-and-nhe3-activity-in-renal-proximal-tubules
#15
Alana N Godinho, Graciana T Costa, Nádia O Oliveira, Bruno A Cardi, Daniel Esdras A Uchoa, Edilberto R Silveira, Luis Eduardo M Quintas, François G Noël, Manassés C Fonteles, Krishnamurti M Carvalho, Cláudia F Santos, Lucília M A Lessa, Nilberto R F do Nascimento
Cardiotonic steroids (CS) are known as modulators of sodium and water homeostasis. These compounds contribute to the excretion of sodium under overload conditions due to its natriuretic property related to the inhibition of renal Na(+)/K(+)-ATPase (NKA) pump α1 isoform. NHE3, the main route for Na(+) reabsorption in the proximal tubule, depends on the Na(+) gradient generated by NKA pump. In the present study we aimed to investigate the effects of marinobufagin (MBG) and telocinobufagin (TBG) on the renal function of isolated perfused rat kidney and on the inhibition of NKA activity...
May 12, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28506695/d816v-mutation-in-the-kit-gene-activation-loop-has-a-greater-cell-proliferative-and-anti-apoptotic-ability-than-n822k-mutation-in-core-binding-factor-acute-myeloid-leukemia
#16
Ikuko Omori, Hiroki Yamaguchi, Koichi Miyake, Noriko Miyake, Tomoaki Kitano, Koiti Inokuchi
In core binding factor-acute myeloid leukemia (CBF-AML), there have been conflicting reports regarding the status as an unfavorable prognostic factor of mutation in the KIT gene, whose significance therefore remains unclear. We have reported previously that prognosis differs between the KIT D816V and N822K mutations. In the present study, we undertook an in vitro comparison of the cell-proliferative and anti-apoptotic ability of D816V and N822K. We transduced these KIT mutations into the IL-3-dependent cell line TF-1 (TF-1 KIT(D816V), TF-1 KIT(N822K))...
May 12, 2017: Experimental Hematology
https://www.readbyqxmd.com/read/28504694/the-prohibitin-repressive-interaction-with-e2f1-is-rapidly-inhibited-by-androgen-signalling-in-prostate-cancer-cells
#17
S Koushyar, G Economides, S Zaat, W Jiang, C L Bevan, D A Dart
Prohibitin (PHB) is a tumour suppressor molecule with pleiotropic activities across several cellular compartments including mitochondria, cell membrane and the nucleus. PHB and the steroid-activated androgen receptor (AR) have an interplay where AR downregulates PHB, and PHB represses AR. Additionally, their cellular locations and chromatin interactions are in dynamic opposition. We investigated the mechanisms of cell cycle inhibition by PHB and how this is modulated by AR in prostate cancer. Using a prostate cancer cell line overexpressing PHB, we analysed the gene expression changes associated with PHB-mediated cell cycle arrest...
May 15, 2017: Oncogenesis
https://www.readbyqxmd.com/read/28502904/src-and-syk-contribute-to-the-anti-inflammatory-activities-of-achyranthes-aspera-ethanolic-extract
#18
Jeong-Ook Lee, Woo Seok Yang, Jae Gwang Park, Deok Jeong, Han Gyung Kim, Kee Dong Yoon, Adithan Aravinthan, Jong-Hoon Kim, Eunji Kim, Jae Youl Cho
ETHNOPHARMACOLOGICAL RELEVANCE: Nuclear factor-kappa B (NF-κB) plays pivotal roles in inflammation. Src and Syk are two tyrosine kinases that act upstream of NF-κB signaling. Although Achyranthes aspera L. (A. aspera) has been used as a traditional medicine to treat fevers and inflammatory ailments and heal wounds, the molecular mechanisms of its anti-inflammatory actions are not yet fully understood. MATERIALS AND METHODS: In this study, we evaluated the anti-inflammatory effect of A...
May 11, 2017: Journal of Ethnopharmacology
https://www.readbyqxmd.com/read/28500298/zbp1-phosphorylation-at-serine-181-regulates-its-dendritic-transport-and-the-development-of-dendritic-trees-of-hippocampal-neurons
#19
Anna S Urbanska, Aleksandra Janusz-Kaminska, Katarzyna Switon, Alicia L Hawthorne, Malgorzata Perycz, Malgorzata Urbanska, Gary J Bassell, Jacek Jaworski
Local protein synthesis occurs in axons and dendrites of neurons, enabling fast and spatially restricted responses to a dynamically changing extracellular environment. Prior to local translation, mRNA that is to be translated is packed into ribonucleoprotein particles (RNPs) where RNA binding proteins ensure mRNA silencing and provide a link to molecular motors. ZBP1 is a component of RNP transport particles and is known for its role in the local translation of β-actin mRNA. Its binding to mRNA is regulated by tyrosine 396 phosphorylation, and this particular modification was shown to be vital for axonal growth and dendritic branching...
May 12, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28498896/inhibition-of-prdm14-expression-in-pancreatic-cancer-suppresses-cancer-stem-like-properties-and-liver-metastasis-in-mice
#20
Chiharu Moriya, Hiroaki Taniguchi, Kanjiro Miyata, Nobuhiro Nishiyama, Kazunori Kataoka, Kohzoh Imai
Pancreatic cancer is one of the most lethal types of cancer, with aggressive properties characterized by metastasis, recurrence, and drug resistance. Cancer stem cells are considered to be responsible for these properties. PRDM14, a transcriptional regulator that maintains pluripotency in embryonic stem cells, is overexpressed in some cancers. Here, we assessed PRDM14 expression and the effects of PRDM14 knockdown on cancer stem-like phenotypes in pancreatic cancer. We observed that PRDM14 protein was overexpressed in pancreatic cancer tissues compared with normal pancreatic tissues...
May 12, 2017: Carcinogenesis
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