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https://www.readbyqxmd.com/read/27881786/neuronal-dysfunction-in-ipsc-derived-medium-spiny-neurons-from-chorea-acanthocytosis-patients-is-reversed-by-src-kinase-inhibition-and-f-actin-stabilization
#1
Nancy Stanslowsky, Peter Reinhardt, Hannes Glass, Norman Kalmbach, Maximilian Naujock, Niko Hensel, Verena Lübben, Arun Pal, Anna Venneri, Francesca Lupo, Lucia De Franceschi, Peter Claus, Jared Sterneckert, Alexander Storch, Andreas Hermann, Florian Wegner
: Chorea-acanthocytosis (ChAc) is a fatal neurological disorder characterized by red blood cell acanthocytes and striatal neurodegeneration. Recently, severe cell membrane disturbances based on depolymerized cortical actin and an elevated Lyn kinase activity in erythrocytes from ChAc patients were identified. How this contributes to the mechanism of neurodegeneration is still unknown. To gain insight into the pathophysiology, we established a ChAc patient-derived induced pluripotent stem cell model and an efficient differentiation protocol providing a large population of human striatal medium spiny neurons (MSNs), the main target of neurodegeneration in ChAc...
November 23, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/27867260/tracking-sentence-comprehension-test-retest-reliability-in-people-with-aphasia-and-unimpaired-adults
#2
Jennifer E Mack, Andrew Zu-Sern Wei, Stephanie Gutierrez, Cynthia K Thompson
PURPOSE: Visual-world eyetracking is increasingly used to investigate online language processing in normal and language impaired listeners. Tracking changes in eye movements over time also may be useful for indexing language recovery in those with language impairments. Therefore, it is critical to determine the test-retest reliability of results obtained using this method. METHODS: Unimpaired young adults and people with aphasia took part in two eyetracking sessions spaced about one week apart...
November 2016: Journal of Neurolinguistics
https://www.readbyqxmd.com/read/27802416/src-kinases-regulate-glutamatergic-input-to-hypothalamic-presympathetic-neurons-and-sympathetic-outflow-in-hypertension
#3
Xin Qiao, Jing-Jing Zhou, De-Pei Li, Hui-Lin Pan
The elevated sympathetic outflow associated with hypertension is maintained by increased N-methyl-d-aspartate receptor (NMDAR) activity in the paraventricular nucleus (PVN) of the hypothalamus. Synaptic NMDAR activity is tightly regulated by protein kinases, including the Src family of tyrosine kinases. We determined whether Src kinases play a role in increased NMDAR activity of PVN neurons projecting to the rostral ventrolateral medulla and in elevated sympathetic vasomotor tone in spontaneously hypertensive rats (SHRs)...
October 31, 2016: Hypertension
https://www.readbyqxmd.com/read/27796759/increased-src-family-kinase-activity-disrupts-excitatory-synaptic-transmission-and-impairs-remote-fear-memory-in-forebrain-shp2-deficient-mice
#4
Xunyi Yan, Bin Zhang, Wen Lu, Lin Peng, Qian Yang, Wei Cao, Shen Lin, Wenyue Yu, Xiaoming Li, Yuehai Ke, Shengtian Li, Wei Yang, Jianhong Luo
Src homolog domain-containing phosphatase 2 (Shp2) signals a variety of cellular and physiological functions including learning and memory. Dysregulation of ERK signaling is known to be responsible for the cognitive deficits associated with gain-of-function mutated Shp2 mimicking Noonan syndrome. However, here, we report that CaMKIIα-cre induced knockout (CaSKO) of Shp2 in hippocampal pyramidal neurons resulted in increased Src activity, upregulated phosphorylation of N-methyl-D-aspartate receptors (NMDARs) at Y1325 of GluN2A and at Y1472 of GluN2B, disrupted the balance of synaptic transmission, and impaired long-term potentiation and remote contextual fear memory...
October 29, 2016: Molecular Neurobiology
https://www.readbyqxmd.com/read/27793680/purification-physico-chemical-characterization-and-thermodynamics-of-chitooligosaccharide-binding-to-cucumber-cucumis-sativus-phloem-lectin
#5
Pavan Kumar Nareddy, Kishore Babu Bobbili, Musti J Swamy
A chitooligosaccharide-specific lectin has been purified from the phloem exudate of cucumber (Cucumis sativus) by affinity chromatography on chitin. The molecular weight of the cucumber phloem lectin (CPL) was determined as 51912.8Da by mass spectrometry whereas SDS-PAGE yielded a single band with a subunit mass of 26kDa, indicating that the protein is a homodimer. Peptide mass fingerprinting studies strongly suggest that CPL is identical to the 26kDa phloem protein 2 (PP2) from cucumber. CD spectroscopy indicated that CPL is a predominantly β-sheets protein...
October 25, 2016: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/27784696/serine-threonine-phosphatases-and-aquaporin-2-regulation-in-renal-collecting-duct
#6
Sophia LeMaire, Viswanathan Raghuram, Cameron R Grady, Christina M Pickering, Chung-Lin Chou, Ezigbobiara N Umejiego, Mark A Knepper
Phosphorylation of the aquaporin-2 (AQP2) water channel at four COOH-terminal serines plays a central role in the regulation of water permeability of the renal collecting duct. The level of phosphorylation at these sites is determined by a balance between phosphorylation by protein kinases and dephosphorylation by phosphatases. The phosphatases that dephosphorylate AQP2 have not been identified. Here, we use large-scale data integration techniques to identify serine-threonine phosphatases likely to interact with AQP2 in renal collecting duct principal cells...
October 26, 2016: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/27748887/gefitinib-enhances-oxaliplatin-induced-apoptosis-mediated-by-src-and-pkc-modulated-gap-junction-function
#7
Jian-Feng Wu, Jie Ji, Shu-Ying Dong, Bei-Bei Li, Mei-Ling Yu, Dan-Dan Wu, Liang Tao, Xu-Hui Tong
Chemotherapeutic drug-induced apoptosis is enhanced by gap junction intercellular communication (GJIC) in a variety of tumor cells. Oxaliplatin and gefitinib are the most widely used chemotherapeutic drugs. However, the synergistic influence remains unknown in testicular cancer chemotherapy. The aim of the present study was to investigate the apoptosis induced by oxaliplatin combined with gefitinib and the potential mechanisms in I-10 testicular cancer cells. The results showed that gefitinib significantly enhanced oxaliplatin-induced apoptosis...
October 11, 2016: Oncology Reports
https://www.readbyqxmd.com/read/27748819/src-tyrosine-kinase-mediates-endothelin-1-induced-early-growth-response-protein-1-expression-via-map-kinase-dependent-pathways-in-vascular-smooth-muscle-cells
#8
Estelle R Simo-Cheyou, George Vardatsikos, Ashok K Srivastava
We have previously demonstrated that the non-receptor protein tyrosine kinase (NR-PTK) c-Src is an upstream regulator of endothelin-1 (ET-1) and angiotensin II-induced activation of protein kinase B (PKB) signaling in vascular smooth muscle cells (VSMCs). We have also demonstrated that ET-1 potently induces the expression of the early growth response protein-1 (Egr-1), a zinc finger transcription factor that is overexpressed in models of vascular diseases, such as atherosclerosis. However, the involvement of c-Src in ET-1‑induced Egr-1 expression has not yet been investigated and its role in mitogen-activated protein kinase (MAPK) signaling remains controversial...
October 6, 2016: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/27748508/src-family-kinase-links-insulin-signaling-to-short-term-regulation-of-na-k-atpase-in-nonpigmented-ciliary-epithelium
#9
Mohammad Shahidullah, Amritlal Mandal, Nicholas A Delamere
Insulin has been shown to elicit changes of Na,K-ATPase activity in various tissues. Na,K-ATPase in the nonpigmented ciliary epithelium (NPE) plays a role in aqueous humor secretion and changes of Na,K-ATPase activity impact the driving force. Because we detect a change of NPE Na,K-ATPase activity in response to insulin, studies were carried out to examine the response mechanism. Ouabain-sensitive rubidium (Rb) uptake by cultured NPE cells, measured as a functional index of Na,K-ATPase-mediated inward potassium transport, was found to increase in cells exposed for 5 min to insulin...
October 17, 2016: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/27742830/lck-inhibits-heat-shock-protein-65-mediated-reverse-cholesterol-transport-in-t-cells
#10
Tiantian Luo, Jing Hu, Dan Xi, Haowei Xiong, Wenshuai He, Jichen Liu, Menghao Li, Hao Lu, Jinzhen Zhao, Wenyan Lai, Zhigang Guo
Previously, we reported that heat shock protein (HSP)65 impairs the effects of high-density lipoprotein on macrophages. We also showed that immune response activation adversely affects reverse cholesterol transport (RCT). In this study, we investigated the effects of the Src family kinase lymphocyte-specific protein tyrosine kinase (Lck) and elucidated the mechanism underlying HSP65-regulated cholesterol efflux in T cells. We evaluated cell proliferation, Lck expression, and inflammatory cytokine production in Jurkat cells and CD4(+) T cells...
October 14, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/27725847/inhibition-of-osteopontin-reduce-the-cardiac-myofibrosis-in-dilated-cardiomyopathy-via-focal-adhesion-kinase-mediated-signaling-pathway
#11
Hui Zhao, Wei Wang, Jie Zhang, Tuo Liang, Guang-Pu Fan, Zhi-Wei Wang, Pei-De Zhang, Xu Wang, Jing Zhang
BACKGROUND: Osteopontin (OPN) is a pleiotropic cytokine, which has been shown to a close relationship with cardiac fibrosis. Overexpression of OPN in cardiomyocytes induces dilated cardiomyopathy (DCM). This research is to study whether inhibition of OPN could reduce myocardial remodelling in DCM, and if this process is focal adhesion kinase (FAK) dependent, which is recently found an important signal molecule in fibrosis. METHOD: Eight-week-old cTnTR(141W) transgenic mouse of DCM were injected with OPN-shRNA in left ventricular free wall, which could inhibit the OPN expression...
2016: American Journal of Translational Research
https://www.readbyqxmd.com/read/27711707/prediction-of-proton-affinities-of-organic-molecules-using-the-any-particle-molecular-orbital-second-order-proton-propagator-approach
#12
Laura Pedraza-González, Jonathan Romero, Jorge Alí-Torres, Andrés Reyes
We assess the performance of the recently developed any-particle molecular-orbital second-order proton propagator (APMO/PP2) scheme [M. Díaz-Tinoco, J. Romero, J. V. Ortiz, A. Reyes and R. Flores-Moreno, J. Chem. Phys., 2013, 138, 194108] on the calculation of gas phase proton affinities (PAs) of a set of 150 organic molecules comprising several functional groups: amines, alcohols, aldehydes, amides, ketones, esters, ethers, carboxylic acids and carboxylate anions. APMO/PP2 PAs display an overall mean absolute error of 0...
October 5, 2016: Physical Chemistry Chemical Physics: PCCP
https://www.readbyqxmd.com/read/27700064/protein-kinase-c-signaling-in-adenoviral-infection
#13
Mohammad Abu Yousuf, Ji Sun Lee, Xiaohong Zhou, Mirja Ramke, Jeong Yoon Lee, James Chodosh, Jaya Rajaiya
Activation of protein kinase C (PKC), a serine/threonine protein kinase, ubiquitously influences cellular signal transduction, and has been shown to play a role in viral entry. In this study, we explored a role for PKC in human adenovirus type 37 infection of primary human corneal fibroblasts, a major target cell for infection. We sought evidence for an interaction between PKC activation and two potential downstream targets: cSrc kinase, shown previously to play a critical role in adenovirus signaling in these cells, and caveolin-1, reported earlier to be important to entry of adenovirus type 37...
October 4, 2016: Biochemistry
https://www.readbyqxmd.com/read/27682013/regulation-of-siglec-8-induced-intracellular-reactive-oxygen-species-production-and-eosinophil-cell-death-by-src-family-kinases
#14
Gen Kano, Bruce S Bochner, Nives Zimmermann
RATIONALE: Siglec-8 is a surface receptor predominantly expressed on human eosinophils where its ligation induces reactive oxygen species (ROS) formation and cell death. Since Siglec-8 has intracellular tyrosine-based motifs, we hypothesized that Src family kinases (SFKs) are involved in ROS formation and cell death induced by Siglec-8 engagement. METHODS: Human peripheral blood eosinophils were purified and incubated with anti-Siglec-8 monoclonal antibodies (mAb, agonist), IL-5, and SFK pharmacological inhibitors...
September 20, 2016: Immunobiology
https://www.readbyqxmd.com/read/27671303/tgf-%C3%AE-signal-transduction-in-pancreatic-carcinoma-cells-is-sensitive-to-inhibition-by-the-src-tyrosine-kinase-inhibitor-azm475271
#15
Tobias Bartscht, Benjamin Rosien, Dirk Rades, Roland Kaufmann, Harald Biersack, Hendrik Lehnert, Hendrik Ungefroren
BACKGROUND: Earlier results from our group have shown that in pancreatic ductal adenocarcinoma (PDAC)-derived cells transforming growth factor (TGF)-β1-dependent epithelial-mesenchymal transition (EMT) and cell motility was inhibited by the Src inhibitors PP2 and PP1 both of which targeted the TGF-β receptors for inhibition. OBJECTIVE: In this study we evaluated the impact of another Src inhibitor, AZM475271, on various TGF-β responses in PDAC cells. METHOD: The effect of AZM475271 on TGF-β1-induced random cell migration (chemokinesis), the expression of EMT and migration/invasion-associated genes, TGF-β-induced luciferase activity, and C-terminal phosphorylation of Smad2 and Smad3 was measured in the PDAC-derived Panc-1 and Colo357 cell lines using real-time cell migration assays, quantitative real-time PCR, luciferase reporter gene assays and phosphoimmunoblotting, respectively...
September 26, 2016: Anti-cancer Agents in Medicinal Chemistry
https://www.readbyqxmd.com/read/27638545/smooth-muscle-contraction-and-growth-of-stromal-cells-in-the-human-prostate-are-both-inhibited-by-the-src-family-kinase-inhibitors-azm475271-and-pp2
#16
Yiming Wang, Christian Gratzke, Alexander Tamalunas, Beata Rutz, Anna Ciotkowska, Frank Strittmatter, Annika Herlemann, Sophie Janich, Raphaela Waidelich, Chunxiao Liu, Christian G Stief, Martin Hennenberg
BACKGROUND AND PURPOSE: In benign prostatic hyperplasia, increased prostate smooth muscle tone and prostate volume may contribute alone or together to urethral obstruction and voiding symptoms. Consequently, connections between smooth muscle tone and growth in the prostate have been assumed, but any molecular basis for such a link is poorly understood. Here, we examined effects of Src family kinase (SFKs) inhibitors on prostate smooth muscle contraction, and growth of stromal cells. EXPERIMENTAL APPROACH: Different SFK inhibitors (AZM475271, PP2) were applied to human prostate tissues to assess effects on smooth muscle contraction, and to cultured stromal cells (WPMY-1) and c-Src-deficient cells, to examine effects on proliferation, actin organization, and viability...
September 17, 2016: British Journal of Pharmacology
https://www.readbyqxmd.com/read/27624844/inhibition-of-src-family-kinases-improves-cognitive-function-after-intraventricular-hemorrhage-or-intraventricular-thrombin
#17
Da Zhi Liu, Ben Waldau, Bradley P Ander, Xinhua Zhan, Boryana Stamova, Glen C Jickling, Bruce G Lyeth, Frank R Sharp
Intraventricular hemorrhage causes spatial memory loss, but the mechanism remains unknown. Our recent studies demonstrated that traumatic brain injury activates Src family kinases, which cause spatial memory loss. To test whether the spatial memory loss was due to blood in the ventricles, which activated Src family kinases, we infused autologous whole blood or thrombin into the lateral ventricles of adult rats to model non-traumatic intraventricular hemorrhage. Hippocampal neuron loss was examined 1 day to 5 weeks later...
September 13, 2016: Journal of Cerebral Blood Flow and Metabolism
https://www.readbyqxmd.com/read/27606882/ouabain-modulates-the-distribution-of-connexin-43-in-epithelial-cells
#18
Arturo Ponce, Isabel Larre, Aida Castillo, Catalina Flores-Maldonado, Odette Verdejo-Torres, Ruben Gerardo Contreras, Marcelino Cereijido
BACKGROUND/AIMS: The fact that ouabain has been identified as an endogenous substance, led us to inquire its physiological role in epithelial cells. Based on previous observations, we hypothesized that it influences processes related to cell contacts. Previously we have shown that nanomolar concentrations of ouabain up-regulate tight junctions, accelerate ciliogenesis, and increase gap junctional intercellular communication (GJIC). Given that silencing assays indicated that connexin 43 (Cnx43) is involved in the GJIC response, in the present work we study whether ouabain affects Cnx43 expression and distribution...
2016: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/27586187/formulation-of-hydrophobic-therapeutics-with-self-assembling-peptide-and-amino-acid-a-new-platform-for-intravenous-drug-delivery
#19
Shaun Pacheco, Takashi Kanou, Shan-Yu Fung, Kenny Chen, Daiyoon Lee, Xiaohui Bai, Shaf Keshavjee, Mingyao Liu
Clinical application of hydrophobic therapeutics is restricted by lack of an efficient vehicle which permits their solubility in aqueous environments. We have previously developed a novel formulation strategy to deliver a hydrophobic Src inhibitor, PP2, involving combinations of one self-assembling peptide (SAP) and one of 4 selected amino acids (AAs). The present study aims to develop a generalized drug delivery platform for intravenous application of hydrophobic drugs by combining self-assembling peptide, amino acid and low concentration of co-solvent...
October 10, 2016: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/27572515/high-mobility-group-box-protein-1-boosts-endothelial-albumin-transcytosis-through-the-rage-src-caveolin-1-pathway
#20
Dan Shang, Tao Peng, Shanmiao Gou, Yiqing Li, Heshui Wu, Chunyou Wang, Zhiyong Yang
High-mobility group box protein 1 (HMGB1), an inflammatory mediator, has been reported to destroy cell-cell junctions, resulting in vascular endothelial hyperpermeability. Here, we report that HMGB1 increases the endothelial transcytosis of albumin. In mouse lung vascular endothelial cells (MLVECs), HMGB1 at a concentration of 500 ng/ml or less did not harm cell-cell junctions but rapidly induced endothelial hyperpermeability to (125)I-albumin. HMGB1 induced an increase in (125)I-albumin and AlexaFluor 488-labeled albumin internalization in endocytosis assays...
August 30, 2016: Scientific Reports
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