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Elena V Bouzinova, Lise Hangaard, Christian Staehr, Aleksandra Mazur, Avelino Ferreira, Alexander Chibalin, Shaun L Sandow, Zijian Xie, Christian Aalkjaer, Vladimir V Matchkov
AIMS: The Na,K-ATPase is involved in a large number of regulatory activities including cSrc-dependent signalling. Upon inhibition of the Na,K-ATPase with ouabain, cSrc activation is shown to occur in many cell types. This study tests the hypothesis that acute potentiation of agonist-induced contraction by ouabain is mediated through Na,K-ATPase-cSrc signalling-dependent sensitization of vascular smooth muscle cells to Ca2+ . METHODS: Agonist-induced rat mesenteric small artery contraction was examined in vitro under isometric conditions and in vivo in anaesthetized rats...
February 26, 2018: Acta Physiologica
Priyanka Grover, Sritama Nath, Monica D Nye, Ru Zhou, Mohammad Ahmad, Pinku Mukherjee
Pancreatic Ductal Adenocarcinoma (PDA) has a mortality rate that nearly matches its incidence rate. Transforming Growth Factor Beta (TGF-β) is a cytokine with a dual role in tumor development switching from a tumor suppressor to a tumor promoter. There is limited knowledge of how TGF-β function switches during tumorigenesis. Mucin 1 (MUC1) is an aberrantly glycosylated, membrane-bound, glycoprotein that is overexpressed in >80% of PDA cases and is associated with poor prognosis. In PDA, MUC1 promotes tumor progression and metastasis via signaling through its cytoplasmic tail (MUC1-CT) and interacting with other oncogenic signaling molecules...
January 23, 2018: Oncotarget
Layla El Moussawi, Mohamed Chakkour, Sawsan I Kreydiyyeh
Epinephrine, a key stress hormone, is known to affect ion transport in the colon. Stress has been associated with alterations in colonic functions leading to changes in water movements manifested as diarrhea or constipation. Colonic water movement is driven by the Na+-gradient created by the Na+/K+-ATPase. Whether epinephrine acts via an effect on the Na+/K+-ATPase hasn't been studied before. The aim of this work was to investigate the effect of epinephrine on the Na+/K+-ATPase and to elucidate the signaling pathway involved using CaCo-2 cells as a model...
2018: PloS One
Jacqueline R Ha, Ryuhjin Ahn, Harvey W Smith, Valerie Sabourin, Steven Hėbert, Eduardo Cepeda Cañedo, Young Kyuen Im, Claudia Kleinman, William J Muller, Josie Ursini-Siegel
The commonality between most phospho-tyrosine signaling networks is their shared use of adaptor proteins to transduce mitogenic signals. ShcA (SHC1) is one such adaptor protein that employs two phospho-tyrosine binding domains (PTB and SH2) and key phospho-tyrosine residues to promote mammary tumorigenesis. Receptor tyrosine kinases (RTKs), such as ErbB2, engage the ShcA PTB domain to promote breast tumorigenesis by engaging Grb2 downstream of the ShcA tyrosine phosphorylation sites to activate AKT/mTOR signaling...
February 16, 2018: Molecular Cancer Research: MCR
Liang-Xing Fang, Xing-Ping Li, Guo-Hui Deng, Shu-Min Li, Run-Shi Yang, Zuo-Wei Wu, Xiao-Ping Liao, Jian Sun, Ya-Hong Liu
We report a novel fusion plasmid pP2-3T co-integrating ST3-IncHI2 with IncFII plasmid backbone mediating multidrug resistance and virulence. Phylogenetic analysis and comparative genomic revealed that pP2-3T and other MDR ST3-IncHI2 plasmids clustered together representing a unique IncHI2 lineage that exhibited high conservation in backbones of plasmid, but possessed highly genetic plasticity in variable regions via acquiring numerous ARGs and fusing with other plasmids. Surveillance studies should be taken to monitor multiresistance IncHI2 plasmids among Enterobacteriaceae...
February 5, 2018: Antimicrobial Agents and Chemotherapy
Lin Tao, Yue Zhu
Several studies have indicated a relationship between melatonin and idiopathic scoliosis, including our previous work which demonstrated that melatonin can inhibit osteoblast proliferation; however, the mechanism remains unclear. Here, we utilized a MTT assay to show that melatonin significantly reduces osteoblast proliferation in a concentration-and time-dependent manner. Through a combination of techniques, including real-time PCR, MTT assays, immunofluorescence, and luciferase assays, we confirmed that melatonin-induced changes in phosphorylated cAMP response element-binding protein (CREB) reduced transcriptional activity in a melatonin receptor-dependent manner...
2018: American Journal of Translational Research
Lucas Taoro-Gonzalez, Yaiza M Arenas, Andrea Cabrera-Pastor, Vicente Felipo
BACKGROUND: Hyperammonemic rats reproduce the cognitive alterations of patients with hepatic encephalopathy, including altered spatial memory, attributed to altered membrane expression of AMPA receptor subunits in hippocampus. Neuroinflammation mediates these cognitive alterations. We hypothesized that hyperammonemia-induced increase in IL-1β in hippocampus would be responsible for the altered GluA1 and GluA2 membrane expression. The aims of this work were to (1) assess if increased IL-1β levels and activation of its receptor are responsible for the changes in GluA1 and/or GluA2 membrane expression in hyperammonemia and (2) identify the mechanisms by which activation of IL-1 receptor leads to altered membrane expression of GluA1 and GluA2...
February 8, 2018: Journal of Neuroinflammation
Beom-June Kwon, Dae-Won Kim, Mahn-Won Park, Sung-Ho Her, Ha Wook Park, Kiyuk Chang, Wook-Sung Chung, Ki-Bae Seung, Tai-Ho Rho
BACKGROUND: This study is the first study to evaluate clinical significance of combined glucose intolerance (CGI) in treatment-naïve hypertensive patients. METHODS: We compared the results of demographic, anthropometric, clinical, laboratory examinations, echocardiography, arterial stiffness, central blood pressure (BP) and ambulatory BP monitoring (ABPM) between the groups according to fasting blood sugar (FBS), postprandial 2 hour blood glucose (PP2) and gender in treatment-naïve hypertensive patients...
February 2, 2018: Clinical and Experimental Hypertension: CHE
Tsuneo Takenaka, Hiromichi Suzuki, Kazuo Eguchi, Hiroshi Miyashita, Kazuyuki Shimada
The progression of chronic kidney disease (CKD) inverts the arterial stiffness gradient. However, central hemodynamic pressure profiles in CKD have not been fully examined. A cross-sectional study was performed to assess the relationship between the CKD stage and central hemodynamic processes. The study enrolled 2020 hypertensive patients who had undergone echocardiography and measurement of their serum creatinine levels. Radial tonometry was applied to all patients to measure central blood pressure. Patients were classified according to six CKD stages based on their estimated glomerular filtration rate...
January 30, 2018: Hypertension Research: Official Journal of the Japanese Society of Hypertension
Yuan Zhao, Qian Li, Xue-Yan Li, Peng Cui, Feng Gao, Ke Zhu, Ling-Zhu Li, Xing-Huai Sun, Zhongfeng Wang
EphB/ephrinB reverse signaling is involved in retinal ganglion cell (RGC) apoptosis in experimental glaucoma. Here, we further investigated the mechanisms underlying EphB/ephrinB reverse signaling activation induced RGC apoptosis in a rat chronic ocular hypertension (COH) model, using patch-clamp techniques in retinal slices. In COH retinas, RGCs showed higher spontaneous firing frequency and much more depolarized membrane potential as compared to control, which was mimicked by intravitreally injection of EphB2-Fc, an activator of ephrinB2...
January 20, 2018: Brain Research
Kishore Babu Bobbili, Debparna Datta, Saradamoni Mondal, Sirilatha Polepalli, Michael Mormann, Musti J Swamy
PP2-like chitin binding phloem exudate lectins, abundant in the sieve tube of cucurbits, have been implicated to play key roles in wound sealing and antipathogenic responses of the plant. Here we report the affinity purification, macromolecular characterization and carbohydrate binding properties of a new chitooligosaccharide-specific lectin from the phloem exudate of ivy gourds (Coccinia indica). The protein, CIA24, has a subunit mass of 24 kDa. Partial sequence analysis indicated that CIA24 exhibits high homology with CIA17 and other Cucurbitaceae PP2 proteins whereas CD spectroscopic studies suggested that β-sheets constitute the predominant secondary structure...
January 13, 2018: International Journal of Biological Macromolecules
Yinna Wang, Alyssa C Rezey, Ruping Wang, Dale D Tang
BACKGROUND: Airway smooth muscle contraction is critical for maintenance of appropriate airway tone, and has been implicated in asthma pathogenesis. Smooth muscle contraction requires an "engine" (myosin activation) and a "transmission system" (actin cytoskeletal remodeling). However, the mechanisms that control actin remodeling in smooth muscle are not fully elucidated. The adapter protein Crk-associated substrate (CAS) regulates actin dynamics and the contraction in smooth muscle. In addition, profilin-1 (Pfn-1) and Abelson tyrosine kinase (c-Abl) are also involved in smooth muscle contraction...
January 5, 2018: Respiratory Research
Sung Yeon Park, Jong-Wan Park, Gun-Woo Lee, Lan Li, Yang-Sook Chun
BACKGROUND: Protein neddylation is a post-translational modification by a covalent conjugation with the neural precursor cell expressed, developmentally downregulated 8 (NEDD8). Although this process has been reported to participate in diverse cellular signaling, little is known about its role in cancer cell migration. Given a recent proteomics report showing that NEDD8 is downregulated in prostate cancer tissues versus normal prostate tissues, we tested the possibility that neddylation plays a role in cancer evolution, and then tried to identify target proteins of the neddylation...
January 5, 2018: BMC Cancer
Panagiotis Kratimenos, Ioannis Koutroulis, Beamon Agarwal, Stamatios Theocharis, Maria Delivoria-Papadopoulos
We have previously shown that cerebral Hypoxia-ischemia (HI) results in activation of Src kinase in the newborn piglet brain. We investigated the regulatory mechanism by which the pre-apoptotic proteins translocate from mitochondria to the cytosol during HI through the Src kinase. Newborn piglets were divided into 3 groups (n = 5/group): normoxic (Nx), HI and HI pre-treated with Src kinase inhibitor PP2 (PP2 + HI). Brain tissue HI was verified by neuropathological analysis and by Adenosine Triphosphate (ATP) and Phosphocreatine (PCr) levels...
November 30, 2017: Scientific Reports
Hui-Feng Hao, Li-Mei Liu, Chun-Shui Pan, Chuan-She Wang, Yuan-Sheng Gao, Jing-Yu Fan, Jing-Yan Han
Objectives: To examine the protective effect of Rhynchophylline (Rhy) on vascular endothelial function in spontaneous hypertensive rats (SHRs) and the underlying mechanism. Methods: Intrarenal arteries of SHRs and Wistar rats were suspended in myograph for force measurement. Expression and phosphorylation of endothelial nitric oxide (NO) synthase (eNOS), Akt, and Src kinase (Src) were examined by Western blotting. NO production was assayed by ELISA. Results: Rhy time- and concentration-dependently improved endothelium-dependent relaxation in the renal arteries from SHRs, but had no effect on endothelium-independent relaxation in SHR renal arteries...
2017: Frontiers in Physiology
Juliana M Navia-Pelaez, Gianne P Campos, Jessica C Araujo-Souza, Nikos Stergiopulos, Luciano S A Capettini
Neuronal nitric oxide synthase (nNOS) is now considered an important player in vascular function. It has a protective role in atherosclerosis and hypertension. However, despite its importance, little is known about the mechanisms that regulate its activity in vascular cells. Here we explore the mechanisms by which nNOS is activated in endothelium. We evaluated aorta relaxation response and phosphorylation of nNOS during protein phosphatases 1 and 2 (PP1 and PP2) inhibition, in eNOS silenced mice. PP1 translocation and interaction between the nuclear inhibitor of PP1 (NIPP1) and PP1 was evaluated in endothelial EA...
January 30, 2018: Nitric Oxide: Biology and Chemistry
John D Tompkins, Todd A Clason, Thomas R Buttolph, Beatrice M Girard, Anne K Linden, Jean C Hardwick, Laura A Merriam, Victor May, Rodney L Parsons
Pituitary adenylate cyclase activating polypeptide (PACAP, Adcyap1) activation of PAC1 receptors (Adcyap1r1) significantly increases excitability of guinea pig cardiac neurons. This modulation of excitability is mediated in part by plasma membrane G protein-dependent activation of adenylyl cyclase and downstream signaling cascades. However, additional mechanisms responsible for the enhanced excitability are activated following internalization of the PAC1 receptor and endosomal signaling. Src family kinases play critical roles mediating endocytosis of many trophic factor and G-protein coupled receptors...
November 15, 2017: American Journal of Physiology. Cell Physiology
Duane Gischewski Pereira, Mariana Alves Resende Salgado, Sayonarah Carvalho Rocha, Hérica L Santos, José Augusto Fp Villar, Ruben G Contreras, Carlos Frederico Leite Fontes, Leandro Augusto Barbosa, Vanessa Faria Cortes
Cisplatin and other platinum-containing drugs have played a crucial role in anticancer treatments for over 30 years. However, treatment with cisplatin may cause serious side effects, such as myelosuppression, nausea, ototoxicity, nephrotoxicity and cell resistance processes. In addition, cardiotonic steroids, particularly digoxin, have recently been suggested to exert potent anticancer effects. Therefore, it is possible that the combined treatment of HeLa cells with cisplatin and digoxin can ameliorate the cytotoxic effects and decrease the side effects of cisplatin...
November 11, 2017: Journal of Cellular Biochemistry
Kishore Babu Bobbili, Gottfried Pohlentz, Akkaladevi Narahari, Kaushal Sharma, A Surolia, Michael Mormann, Musti J Swamy
Phloem protein-2 (PP2) is an abundant soluble protein in the sieve elements in plants. Its lectin property was reported in various species. The primary structure of PP2 from Coccinia indica (Coccinia indica agglutinin, CIA17), determined by mass spectrometry, shows extensive homology with PP2 super family phloem lectins. Analysis of mass spectrometric data indicated the presence of 16 potential allelic variants of CIA17 with insignificant divergence in the primary structure. The primary structure contains an intramolecular disulfide bridge between Cys-34 and Cys-51, which is conserved across various cucurbit species and hence likely to be important for carbohydrate binding...
November 7, 2017: International Journal of Biological Macromolecules
Rinaldo Livio Perri, Marika Berchicci, Valentina Bianco, Donatella Spinelli, Francesco Di Russo
Using two independent electrical neuroimaging techniques (BESA and sLORETA), we tested a fMRI-seeded source modeling indicating that in visual discriminative tasks the anterior insula (aIns) participates in the generation of three prefrontal ERP components: the pN1 (at 115 ms), the pP1 (at 170 ms), and the pP2 (at 300 ms). This latter component represented the focus of the present study. Results showed that the pP2 had different activation profiles across hemispheres. The left aIns activity peaked at 420 ms (30 ms before the response) for both Go and No-go trials, that is independently from the ultimate choice (response or inhibition)...
November 9, 2017: Brain Structure & Function
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