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Cross Talk (cross + talk)
Selected AbstractsPlasticity of perisynaptic astroglia during synaptogenesis in the mature rat hippocampusGLIA, Issue 1 2007Mark R. Witcher Abstract Astroglia are integral components of synapse formation and maturation during development. Less is known about how astroglia might influence synaptogenesis in the mature brain. Preparation of mature hippocampal slices results in synapse loss followed by recuperative synaptogenesis during subsequent maintenance in vitro. Hence, this model system was used to discern whether perisynaptic astroglial processes are similarly plastic, associating more or less with recently formed synapses in mature brain slices. Perisynaptic astroglia was quantified through serial section electron microscopy in perfusion-fixed or sliced hippocampus from adult male Long-Evans rats that were 65,75 days old. Fewer synapses had perisynaptic astroglia in the recovered hippocampal slices (42.4% ± 3.4%) than in the intact hippocampus (62.2% ± 2.6%), yet synapses were larger when perisynaptic astroglia was present (0.055 ± 0.003 ,m2) than when it was absent (0.036 ± 0.004 ,m2) in both conditions. Importantly, the length of the synaptic perimeter surrounded by perisynaptic astroglia and the distance between neighboring synapses was not proportional to synapse size. Instead, larger synapses had longer astroglia-free perimeters where substances could escape from or enter into the synaptic clefts. Thus, smaller presumably newer synapses as well as established larger synapses have equal access to extracellular glutamate and secreted astroglial factors, which may facilitate recuperative synaptogenesis. These findings suggest that as synapses enlarge and release more neurotransmitter, they attract astroglial processes to a discrete portion of their perimeters, further enhancing synaptic efficacy without limiting the potential for cross talk with neighboring synapses in the mature rat hippocampus. © 2006 Wiley-Liss, Inc. [source] Cell adhesion regulates platelet-derived growth factor,induced MAP kinase and PI-3 kinase activation in stellate cellsHEPATOLOGY, Issue 3 2002Vinicio Carloni The biologic effects of growth factors are dependent on cell adhesion, and a cross talk occurs between growth factors and adhesion complexes. The aim of the present study was to evaluate the influence of cell adhesion on the major intracellular signaling pathways elicited by platelet-derived growth factor (PDGF) in hepatic stellate cells (HSC). PDGF signaling was investigated in an experimental condition characterized by lack of cell adhesion for different intervals of time. Basal and PDGF-induced focal adhesion kinase (FAK) tyrosine phosphorylation was maintained in a condition of cell suspension for 2, 4, and 6 hours, whereas it was completely lost after 12 and 24 hours. We examined MAP kinase activity at 2 and 24 hours, corresponding to the higher and lower levels of FAK phosphorylation. In these experiments, MAP kinase activity correlated with FAK phosphorylation. Stimulation with PDGF was able to cause Ras-GTP loading only in adherent cells. The ability of PDGF to induce phosphatidylinositol 3-kinase (PI 3-K) activity was abrogated in cells maintained in suspension. The Ser473 phosphorylation of Akt was only marginally affected by the lack of cell adhesion. We then evaluated the association of FAK with c-Src. This association was found to be cell adhesion dependent, and it did not appear to be dependent from phosphorylated FAK. These changes in PDGF-induced intracellular signaling were associated with a remarkable reduction of PDGF-proliferative potential in nonadherent cells, although no marked differences in the apoptotic rate were observed. In conclusion, these results suggest that cell adhesion differentially regulates major signaling pathways activated by PDGF in HSC. [source] Cyclooxygenase-2 inhibition inhibits PI3K/AKT kinase activity in epithelial ovarian cancerINTERNATIONAL JOURNAL OF CANCER, Issue 2 2010Shahab Uddin Abstract Cyclooxygenase-2 (COX-2) expression contributes to tumor growth and invasion in epithelial ovarian cancer (EOC). COX-2 inhibitors exhibit important anticarcinogenic potential against EOC, but the molecular mechanisms underlying this effect and relation with PI3-kinase/AKT signaling remain the subject of intense investigations. Therefore, the role of COX-2 in EOC and its cross talk with PI3-kinase/AKT pathway were investigated using a large series of EOC tissues in a tissue micro array (TMA) format followed by in vitro and in vivo studies using EOC cell lines and NUDE mice. Clinically, COX-2 was overexpressed in 60.3% of EOC and was significantly associated with activated AKT (p < 0.0001). Cox-1 expression was seen in 59.9% but did not associate with AKT. Our in vitro data using EOC cell line showed that inhibition of COX-2 by aspirin, selective inhibitor NS398 and gene silencing by COX-2 specific siRNA impaired phosphorylation of AKT resulting decreased downstream signaling leading to cell growth inhibition and induction of apoptosis. Finally, treatment of MDAH2774 cell line xenografts with aspirin resulted in growth inhibition of tumors in NUDE mice via down-regulation of COX-2 and AKT activity. These data identify COX-2 as a potential biomarker and therapeutic target in distinct molecular subtypes of ovarian cancer. [source] PELP1: A novel therapeutic target for hormonal cancersIUBMB LIFE, Issue 3 2010Dimple Chakravarty Abstract Recent studies implicate that the estrogen receptor (ER) coregulator proline-, glutamic acid-, and leucine-rich protein (PELP) 1 as playing critical roles in ER-genomic, ER-nongenomic, and ER-signaling cross talk with growth factor signaling pathways. PELP1 expression is deregulated in hormonal cancers and recent studies further elucidated the molecular mechanisms by which PELP1 regulates hormone therapy response. Although PELP1 is important for normal functions of the ER, the possibility to target ER-PELP1 axis appears to be an effective strategy for preventing hormonal carcinogenesis and therapy resistance. Thus, PELP1 may be useful as prognostic marker for hormonal cancers and PELP1 signaling may be useful to generate targeted therapeutics to overcome hormonal therapy resistance. © 2009 IUBMB IUBMB Life, 62(3): 163,169, 2010 [source] Morphological Evidence for Direct Interaction Between Gonadotrophin-Releasing Hormone Neurones and Astroglial Cells in the Human HypothalamusJOURNAL OF NEUROENDOCRINOLOGY, Issue 9 2007M. Baroncini In rodents, there is compelling evidence indicating that dynamic cell-to-cell communications involving cross talk between astroglial cells (such as astrocytes and specialised ependymoglial cells known as tanycytes) and neurones are important in regulating the secretion of gonadotrophin-releasing hormone (GnRH), the neurohormone that controls both sexual maturation and adult reproductive function. However, whether such astroglial cell,GnRH neurone interactions occur in the human brain is not known. In the present study, we used immunofluorescence to examine the anatomical relationship between GnRH neurones and glial cells within the hypothalamus of five women. Double-staining experiments demonstrated the ensheathment of GnRH neurone perikarya by glial fibrillary acidic protein (GFAP)-immunoreactive astrocyte processes in the periventricular zone of the tuberal region of the hypothalamus. GFAP immunoreactivity did not overlap that of GnRH at the GnRH neurone's projection site (i.e. the median eminence of the hypothalamus). Rather, human GnRH neuroendocrine fibres were found to be closely associated with vimentin or nestin-immunopositive radial gial processes likely belonging to tanycytes. In line with these light microscopy data, ultrastructural examination of GnRH-immunoreactive neurones showed numerous glial cells in direct apposition to pre-embedding-labelled GnRH cell bodies and/or dendrites in the infundibular nucleus, whereas postembedding immunogold-labelled GnRH nerve terminals were often seen to be enwrapped by glial cell processes in the median eminence. GnRH nerve button were sometimes visualised in close proximity to fenestrated pituitary portal blood capillaries and/or evaginations of the basal lamina that delineate the pericapillary space. In summary, these data demonstrate that GnRH neurones morphologically interact with astrocytes and tanycytes in the human brain and provide evidence that glial cells may contribute physiologically to the process by which the neuroendocrine brain controls the function of GnRH neurones in humans. [source] Protein phosphatase 2A,negative regulation of the protective signaling pathway of Ca2+/CaM-dependent ERK activation in cerebral ischemiaJOURNAL OF NEUROSCIENCE RESEARCH, Issue 12 2008Jie Zhao Abstract Extracellular-signal-regulated kinase (ERK) undergoes rapid inactivation following the intense activation evoked by cerebral ischemia and reperfusion. However, the precise mechanism of this inactivation has not been elucidated. To investigate how phosphatases regulate the ERK cascade following ischemia, the PP2A inhibitors cantharidin and okadaic acid were administrated to the CA1 subregion of the rat hippocampus. The resulting sustained ERK activity implies that PP2A is a major phosphatase contributing to the rapid inactivation, but not activation, of ERK following cerebral ischemia. The increase in PP2A activity induced by ceramide has a weak effect on the activation of Raf via dephosphorylation of Ser259 in response to ischemia. In contrast, ketamine (Keta) and cyclosporine A (CsA), two chemicals that block calcium signal in ischemia, decrease ERK activity by blocking Raf dephosphorylation of Ser259. We also observed that activation of an upstream protein, Ras-GRF, leads to calcium/calmodulin-dependent activation of the ERK signaling cascade in response to ischemic stimuli. In addition, the activity of cyclic AMP response element-binding protein (CREB) and estrogen receptor , (ER,), target proteins of ERK and protective elements against ischemic lesion, parallels the activity of ERK. These data indicate that PP2A plays a significant role in blocking the protective effect induced by the ERK kinase pathway and that fast inactivation of ERK is the result of cross talk between calcium/calmodulin-dependent, positively regulated signal cascades and a ceramide-dependent negative signaling pathway. © 2008 Wiley-Liss, Inc. [source] Interactions between neural membrane glycerophospholipid and sphingolipid mediators: A recipe for neural cell survival or suicideJOURNAL OF NEUROSCIENCE RESEARCH, Issue 9 2007Akhlaq A. Farooqui Abstract The neural membranes contain phospholipids, sphingolipids, cholesterol, and proteins. Glycerophospholipids and sphingolipids are precursors for lipid mediators involved in signal transduction processes. Degradation of glycerophospholipids by phospholipase A2 (PLA2) generates arachidonic acid (AA) and docosahexaenoic acids (DHA). Arachidonic acid is metabolized to eicosanoids and DHA is metabolized to docosanoids. The catabolism of glycosphingolipids generates ceramide, ceramide 1-phosphate, sphingosine, and sphingosine 1-phosphate. These metabolites modulate PLA2 activity. Arachidonic acid, a product derived from glycerophospholipid catabolism by PLA2, modulates sphingomyelinase (SMase), the enzyme that generates ceramide and phosphocholine. Furthermore, sphingosine 1-phosphate modulates cyclooxygenase, an enzyme responsible for eicosanoid production in brain. This suggests that an interplay and cross talk occurs between lipid mediators of glycerophospholipid and glycosphingolipid metabolism in brain tissue. This interplay between metabolites of glycerophospholipid and sphingolipid metabolism may play an important role in initiation and maintenance of oxidative stress associated with neurologic disorders as well as in neural cell proliferation, differentiation, and apoptosis. Recent studies indicate that PLA2 and SMase inhibitors can be used as neuroprotective and anti-apoptotic agents. Development of novel inhibitors of PLA2 and SMase may be useful for the treatment of oxidative stress, and apoptosis associated with neurologic disorders such as stroke, Alzheimer disease, Parkinson disease, and head and spinal cord injuries. © 2007 Wiley-Liss, Inc. [source] TG101209, a novel JAK2 inhibitor, has significant in vitro activity in multiple myeloma and displays preferential cytotoxicity for CD45+ myeloma cells,AMERICAN JOURNAL OF HEMATOLOGY, Issue 9 2010Vijay Ramakrishnan Interaction of myeloma cells with the bone marrow microenvironment is mediated in large part through different cytokines, especially VEGF and IL6. These cytokines, especially IL6, leads to upregulation of the JAK/STAT pathway in myeloma cell, contributing to increased proliferation, decreased apoptosis, and acquired drug resistance. Here, we examined the preclinical activity of a novel JAK2 inhibitor TG101209. TG101209 induced dose- and time-dependent cytotoxicity in a variety of multiple myeloma (MM) cell lines. The induction of cytotoxicity was associated with inhibition of cell cycle progression and induction of apoptosis in myeloma cell lines and patient-derived plasma cells. Evaluation of U266 cell lines and patient cells, which have a mix of CD45 positive and negative cells, demonstrated more profound cytotoxicity and antiproliferative activity of the drug on the CD45+ population relative to the CD45, cells. Exploring the mechanism of action of TG101209 indicated downregulation of pJak2, pStat3, and Bcl-xl levels with upregulation of pErk and pAkt levels indicating cross talk between signaling pathways. TG101209, when used in combination with the PI3K inhibitor LY294002, demonstrated synergistic cytotoxicity against myeloma cells. Our results provide the rationale for clinical evaluation of TG101209 alone or in combination with PI3K/Akt inhibitors in MM. Am. J. Hematol., 2010. © 2010 Wiley-Liss, Inc. [source] Phytochromes, Cryptochromes, Phototropin: Photoreceptor Interactions in PlantsPHOTOCHEMISTRY & PHOTOBIOLOGY, Issue 1 2000Jorge J. Casal ABSTRACT In higher plants, natural radiation simultaneously activates more than one photoreceptor. Five phytochromes (phyA through phyD), two cryptochromes (cry1, cry2) and phototropin have been identified in the model species Arabidopsis thaliana. There is light-dependent epistasis among certain photoreceptor genes because the action of one pigment can be affected by the activity of others. Under red light, phyA and phyB are antagonistic, but under far-red light, followed by brief red light, phyA and phyB are synergistic in the control of seedling morphology and the expression of some genes during de-etiolation. Under short photoperiods of red and blue light, cry1 and phyB are synergistic, but under continuous exposure to the same light field the actions of phyB and cry1 become independent and additive. Phototropic bending of the shoot toward unilateral blue light is mediated by phototropin, but cry1, cry2, phyA and phyB positively regulate the response. Finally, cry2 and phyB are antagonistic in the induction of flowering. At least some of these interactions are likely to result from cross talk of the photoreceptor signaling pathways and uncover new avenues to approach signal transduction. Experiments under natural radiation are beginning to show that the interactions create a phototransduction network with emergent properties. This provides a more robust system for light perception in plants. [source] Phagocytosis of Apoptotic Trophoblast Cells by Human Endometrial Endothelial Cells Induces Proinflammatory Cytokine ProductionAMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY, Issue 1 2010Bing Peng Citation Peng B, Koga K, Cardenas I, Aldo P, Mor G. Phagocytosis of apoptotic trophoblast cells by human endometrial endothelial cells induces proinflammatory cytokine production. Am J Reprod Immunol 2010; 64: 12,19 Problem, Apoptosis is a normal constituent of trophoblast turnover in the placenta; however in some cases, this process is related to pregnancy complications such as preeclampsia. Recognition and engulfment of these apoptotic trophoblast cells is important for clearance of dying cells. The aim of this study was to show the cross talk between human endometrial endothelial cells (HEECs) and apoptotic trophoblast cells in an in vitro coculture model and its effect on cytokine production by HEECs. Method of study, Fluorescent-labeled HEECs were cocultured with fluorescent-labeled apoptotic human trophoblast cells. Confocal microscopy and flowcytometry were used to show the interaction between these two types of cells. Cytokine profiles were determined using multiplex analysis. Results, HEECs are capable to phagocytose apoptotic trophoblasts. This activity is inhibited by the phagocytosis inhibitor cytochalasin B. Phagocytosis of apoptotic trophoblast cells induced the secretion of the proinflammatory cytokines interleukin-6 and monocyte chemoattractant protein-1 by HEECs. Conclusion, This study provides the first evidence that HEECs have an ability to phagocytose apoptotic trophoblasts. Furthermore, we demonstrated an inflammatory response of HEECs after phagocytosing the apoptotic trophoblast cells. This event may contribute to the inflammatory response in both normal pregnancy and pathologic pregnancy such as preeclampsia. [source] REVIEW ARTICLE: Interleukin-10: A Multi-Faceted Agent of PregnancyAMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY, Issue 6 2010Jessica E. Thaxton Citation Thaxton JE, Sharma S. Interleukin-10: a multi-faceted agent of pregnancy. Am J Reprod Immunol 2010 It is widely accepted that pregnancy constitutes a unique developmental event. Unprecedented intrauterine actions of angiogenesis, immunity, and neuroendocrine regulation are juxtaposed to mechanisms of senescence that enable fetal growth and protection. The suppressive and regulatory factors that facilitate healthy pregnancy are under investigation. In non-pregnant systems of infection and inflammation, the cytokine interleukin-10 (IL-10) has been widely investigated because of its potential as a key immunosuppressant in response to a multitude of inflammatory events. In the context of pregnancy, IL-10 levels increase markedly in women during early pregnancy and remain elevated well into the third trimester immediately prior to onset of labor. The role of IL-10 during pregnancy as a suppressor of active maternal immunity to allow acceptance of the fetal allograft has been a point of study. Moreover, secretion of IL-10 by a diverse set of maternal and fetal cells has proven to aid in the orchestration of normal processes of pregnancy. Interestingly, some of the more profound findings regarding the actions of IL-10 during pregnancy have manifested from research that focuses on aberrant pregnancy outcomes as a result of inflammation, hormonal imbalances, or gene,environment interactions. This review focuses on the role of IL-10 as a facilitator of successful pregnancy both as an immune suppressive agent and a mediator of cross talk between the placenta and the decidua. Importantly, we discuss investigations on adverse pregnancy conditions to further elucidate the multifarious role of IL-10 at the maternal,fetal interface. [source] Wnt Pathway Regulation in Chronic Renal Allograft DamageAMERICAN JOURNAL OF TRANSPLANTATION, Issue 10 2009C. Von Toerne The Wnt signaling pathway, linked to development, has been proposed to be recapitulated during the progressive damage associated with chronic organ failure. Chronic allograft damage following kidney transplantation is characterized by progressive fibrosis and a smoldering inflammatory infiltrate. A modified, Fischer 344 (RT1lvl) to Lewis (RT1l) rat renal allograft model that reiterates many of the major pathophysiologic processes seen in patients with chronic allograft failure was used to study the progressive disease phenotype and specific gene product expression by immunohistochemistry and transcriptomic profiling. Central components of the Tgfb, canonical Wnt and Wnt-Ca2+ signaling pathways were significantly altered with the development of chronic damage. In the canonical Wnt pathway, Wnt3, Lef1 and Tcf1 showed differential regulation. Target genes Fn1, Cd44, Mmp7 and Nos2 were upregulated and associated with the progression of renal damage. Changes in the Wnt-Ca2+ pathway were evidenced by increased expression of Wnt6, Wnt7a, protein kinase C, Cam Kinase II and Nfat transcription factors and the target gene vimentin. No evidence for alterations in the Wnt planar cell polarity (PCP) pathway was detected. Overall results suggest cross talk between the Wnt and Tgfb signaling pathways during allograft inflammatory damage and present potential targets for therapeutic intervention. [source] Carotenoids and retinoids as suppressors on adipocyte differentiation via nuclear receptorsBIOFACTORS, Issue 1-4 2000Teruo Kawada Abstract The adipocyte differentiation program is regulated by the sequential expression of transcriptional activators, mainly peroxisome proliferator activated receptor (PPAR) families. In the present study, we have decided to systematically examine the effects of vitamin A and its precursors, carotenoids and retinoids, on terminal differentiation from preadipocytes to adipocytes on the cellular and molecular aspects. The effects of active form of vitamin A, retinoic acid (RA), are believed to be mediated by specific nuclear receptor proteins [retinoic acid receptor (RAR)] which are members of the steroid and thyroid/retinoid receptor superfamily of ligand dependent transcriptional regulators. RAR,, RAR,, RXR,, and RXR, mRNA were abundant in adipose tissue and 3T3-L1 adipose cells. The autoregulated amplification of RAR, mRNA was observed by these own ligands in 3T3-L1 cells. And, RA inhibited PPAR,2 expression more effectively and caused concomitantly a greater inhibition of adipocyte differentiation. These results suggest that the inhibitory action of adipocyte differentiation by carotenoids and retinoids are exhibited through the RAR up-regulation and the suppression of PPAR,2. The nature of the cross talk of vitamin A actions between the RARs, RXRs and PPARs via co-activator in adipose tissue will likely prove to be important for understanding the process of adipogenesis. [source] Cross talking of network motifs in gene regulation that generates temporal pulses and spatial stripesGENES TO CELLS, Issue 11 2005Shuji Ishihara Gene regulatory networks contain several substructures called network motifs, which frequently exist throughout the networks. One of such motifs found in Escherichia coli, Saccharomyces cerevisiae, and Drosophila melanogaster is the feed-forward loop, in which an effector regulates its target by a direct regulatory interaction and an indirect interaction mediated by another gene product. Here, we theoretically analyze the behavior of networks that contain feed-forward loops cross talking to each other. In response to levels of the effecter, such networks can generate multiple rise-and-fall temporal expression profiles and spatial stripes, which are typically observed in developmental processes. The mechanism to generate these responses reveals the way of inferring the regulatory pathways from experimental results. Our database study of gene regulatory networks indicates that most feed-forward loops actually cross talk. We discuss how the feed-forward loops and their cross talks can play important roles in morphogenesis. [source] | |||||||||||||