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Mediated Signalling (mediated + signalling)
Selected AbstractsContraction-induced changes in skeletal muscle Na+,K+ pump mRNA expression , importance of exercise intensity and Ca2+ -mediated signallingACTA PHYSIOLOGICA, Issue 4 2010N. B. Nordsborg Abstract Aim:, To investigate if exercise intensity and Ca2+ signalling regulate Na+,K+ pump mRNA expression in skeletal muscle. Methods:, The importance of exercise intensity was evaluated by having trained and untrained humans perform intense intermittent and prolonged exercise. The importance of Ca2+ signalling was investigated by electrical stimulation of rat soleus and extensor digitorum longus (EDL) muscles in combination with studies of cell cultures. Results:, Intermittent cycling exercise at ,85% of VO2peak increased (P < 0.05) ,1 and ,1 mRNA expression ,2-fold in untrained and trained subjects. In trained subjects, intermittent exercise at ,70% of VO2peak resulted in a less (P < 0.05) pronounced increase (,1.4-fold; P < 0.05) for ,1 and no change in ,1 mRNA. Prolonged low intensity exercise increased (P < 0.05) mRNA expression of ,1 ,3.0-fold and ,2 ,1.8-fold in untrained but not in trained subjects. Electrical stimulation of rat soleus, but not EDL, muscle increased (P < 0.05) ,1 mRNA expression, but not when combined with KN62 and cyclosporin A incubation. Ionomycin incubation of cultured primary rat skeletal muscle cells increased (P < 0.05) ,1 and reduced (P < 0.001) ,2 mRNA expression and these responses were abolished (P < 0.05) by co-incubation with cyclosporin A or KN62. Conclusion:, (1) Exercise-induced increases in Na+,K+ pump ,1 and ,1 mRNA expression in trained subjects are more pronounced after high- than after moderate- and low-intensity exercise. (2) Both prolonged low and short-duration high-intensity exercise increase ,1 mRNA expression in untrained subjects. (3) Ca2+i regulates ,1 mRNA expression in oxidative muscles via Ca2+/calmodulin-dependent protein kinase (CaMK) and calcineurin signalling pathways. [source] Inositol-requiring 1/X-box-binding protein 1 is a regulatory hub that links endoplasmic reticulum homeostasis with innate immunity and metabolismEMBO MOLECULAR MEDICINE, Issue 6 2010Randal J. Kaufman Abstract Inositol-requiring 1 (IRE1)/X-box-binding protein 1 (XBP1)-mediated signalling represents the most conserved branch of the unfolded protein response. A series of recent studies reveal novel and potentially ancient roles for this pathway in the coordination of metabolic and immune responses. [source] Interleukin-6 Induction by Helicobacter pylori in Human Macrophages is Dependent on PhagocytosisHELICOBACTER, Issue 3 2006Stefan Odenbreit Abstract Background:, The colonization of the gastric mucosa with Helicobacter pylori is accompanied by elevated levels of proinflammatory cytokines, such as interleukin-1 (IL-1), IL-6, and IL-8. The aim of our study was to determine the mechanisms of IL-6 stimulation in phagocytes upon H. pylori infection. Materials and Methods:, We investigated the secretion of IL-6 by different professional phagocytes from murine and human origin, including granulocyte- and monocyte-like cells and macrophages derived from human peripheral blood monocytes (PBMCs). The influence of viability, phagocytosis, and the impact of different subcellular fractions of H. pylori bacteria were evaluated. Results:, IL-6 levels induced by H. pylori were low in cell lines derived from murine and human monocytes and in human granulocyte-like cells. By contrast, macrophages derived from human PBMCs were highly responsive to both H. pylori and Escherichia coli. IL-6 induction was blocked by inhibition of actin-dependent processes prior to infection with H. pylori, but not with E. coli or E. coli lipopolysaccharide (LPS). Using cell fractionation, the most activity was found in the H. pylori membrane. H. pylori LPS exhibited a 103 - to 104 -fold lower biologic activity than E. coli LPS, suggesting a minor role for toll-like receptor 4 (TLR4)-mediated signalling from the exterior. Conclusions:, From these data, we conclude that macrophages may be a major source of IL-6 in the gastric mucosa upon H. pylori infection. The IL-6 induction by H. pylori in these cells is a multifactorial process, which requires the uptake and presumably degradation of H. pylori bacteria. [source] Elucidation of the gating of the GIRK channel using a spectroscopic approachTHE JOURNAL OF PHYSIOLOGY, Issue 22 2009Adi Raveh The traditional view of G protein-coupled receptor (GPCR)-mediated signalling puts the players in this signalling cascade, namely the GPCR, the G protein and its effector, as individual components in space, where the signalling specificity is obtained mainly by the interaction of the GPCR and the G, subunits of the G protein. A question is then raised as to how fidelity in receptor signalling is achieved, given that many systems use the same components of the G protein signalling machinery. One possible mechanism for obtaining the specific flow of the downstream signals, from the activated G protein to its specific effector target, in a timely manner, is compartmentalization, a spatial arrangement of the complex in a rather restricted space. Here we review our recent findings related to these issues, using the G protein-coupled potassium channel (GIRK) as a model effector and fluorescence-based approaches to reveal how the signalling complex is arranged and how the G protein exerts its action to activate the GIRK channel in intact cells. [source] Immunohistochemical detection for nuclear ,-catenin in sporadic basal cell carcinomaBRITISH JOURNAL OF DERMATOLOGY, Issue 5 2001F. Yamazaki Background Despite the increasing incidence of basal cell carcinoma (BCC), its pathogenesis has remained largely unknown. Recently, it was reported that genes involved in tissue morphogenesis, such as sonic hedgehog or patched, were found to be mutated in BCC, suggesting the involvement of those molecules in the pathogenesis of this tumour. Furthermore, there is evidence that the Wnt-mediated signalling pathway may be one of the downstream targets of sonic hedgehog -mediated signalling, which has led us to focus on molecular events on the Wnt pathway in BCC. Among the signal transducers involved in the Wnt pathway, it is clear that ,-catenin plays a pivotal role in the promotion of morphogenesis and cell growth. In respect to this, it has been reported that, in particular circumstances, as in colorectal cancers, ,-catenin migrates to the nuclei, where it exerts an ability to activate the transcription of various genes. Objectives To investigate the cellular distribution of ,-catenin in skin tumours, in particular, in BCC. Methods Twenty skin biopsy specimens derived from BCC, 10 from inflammatory skin diseases and five from squamous cell carcinomas were immunostained with an antibody directed against ,-catenin. Results Fourteen of the 20 BCC samples tested showed nuclear localization of ,-catenin, while none of the other samples gave rise to positive nuclear staining. Conclusions Nuclear localization of ,-catenin is a characteristic feature of BCC; this suggests its tumorigenic role in this tumour. This gives us a further insight into the molecular pathogenesis of BCC. [source] Intermolecular cross-talk between the prostaglandin E2 receptor (EP)3 subtype and thromboxane A2 receptor signalling in human erythroleukaemic cellsBRITISH JOURNAL OF PHARMACOLOGY, Issue 3 2009Helen M Reid Background and purpose:, In previous studies investigating cross-talk of signalling between prostaglandin (PG)E2 receptor (EP) and the TP, and TP, isoforms of the human thromboxane (TX)A2 receptor (TP), 17-phenyl trinor PGE2 -induced desensitization of TP receptor signalling through activation of the AH6809 and SC19220-sensitive EP1 subtype of the EP receptor family, in a cell-specific manner. Here, we sought to further investigate that cross-talk in human erythroleukaemic (HEL) 92.1.7 cells. Experimental approach:, Specificity of 17-phenyl trinor PGE2 signalling and its possible cross-talk with signalling by TP,/TP, receptors endogenously expressed in HEL cells was examined through assessment of agonist-induced inositol 1,4,5-trisphosphate (IP)3 generation and intracellular calcium ([Ca2+]i) mobilization. Key results:, While 17-Phenyl trinor PGE2 led to activation of phospholipase (PL)C, to yield increases in IP3 generation and [Ca2+]i, it did not desensitize but rather augmented that signalling in response to subsequent stimulation with the TXA2 mimetic U46619. Furthermore, the augmentation was reciprocal. Signalling by 17-phenyl trinor PGE2 was found to occur through AH6809- and SC19920-insensitive, Pertussis toxin-sensitive, Gi/G,, -dependent activation of PLC,. Further pharmacological investigation using selective EP receptor subtype agonists and antagonists confirmed that 17-phenyl trinor PGE2 -mediated signalling and reciprocal cross-talk with the TP receptors occurred through the EP3, rather than the EP1, EP2 or EP4 receptor subtype in HEL cells. Conclusions and Implications:, The EP1 and EP3 subtypes of the EP receptor family mediated intermolecular cross-talk to differentially regulate TP receptor-mediated signalling whereby activation of EP1 receptors impaired or desensitized, while that of EP3 receptors augmented signalling through TP,/TP, receptors, in a cell type-specific manner. [source] Phosphoinositide 3-kinase mediated signalling contributes to development of diabetes-induced abnormal vascular reactivity of rat carotid arteryCELL BIOCHEMISTRY AND FUNCTION, Issue 1 2006Mariam H. M. Yousif Abstract Diabetes mellitus is associated with vascular complications, including an impairment of vascular function and alterations in the reactivity of blood vessels to vasoactive agents. Phosphatidylinositol 3-kinase (PI3K) is a signalling enzyme that plays key roles in vascular growth, proliferation and cellular apoptosis and is implicated in modulating vascular smooth muscle contractility. The aim of this study was to determine whether PI3K plays a role in development of diabetes-induced altered vascular reactivity to selected vasoconstrictors and vasodilators. The effect of 2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one (LY294002), a selective PI3K inhibitor, on isolated segments of carotid arteries from streptozotocin (STZ)-diabetic rats was investigated. Ring segments of the isolated carotid arteries were mounted in organ baths to measure changes in isometric tension. Our results showed that STZ treatment produced an increase in the vasoconstrictor response to norepinephrine (NE), angiotensin II (Ang II) and endothelin-1 (ET-1) and an attenuated vasodilator response to carbachol and histamine in the isolated carotid arteries from STZ-diabetic animals. Diabetes-induced impaired vascular responsiveness to the vasoactive agonists was prevented by chronic inhibition of PI3K by LY294002 even though blood glucose levels remained high. This is the first study to show that selective inhibition of PI3K can attenuate the development of diabetes-induced abnormal vascular reactivity in the isolated carotid arteries of diabetic rats. Copyright © 2005 John Wiley & Sons, Ltd. [source] | |||||||||||||