Search results for "KINASE"

Enhanced platelet thromboxane synthesis and reduced macrophage-dependent fibrinolytic activity related to oxidative stress in oral contraceptive-trea…

1996

Abstract In previous studies conducted in rats and in women, we have shown that oral contraceptive (OC) administration induced a platelet hyperaggregation simultaneously with an increased platelet lipid biosynthesis which might be related to lipid peroxidation. In the present study, we specifically studied the arachidonic acid and the fibrinolytic pathways in relation to the fatty acid composition in female rats treated for 6 weeks with OC (ethinyl estradiol plus lynestrenol). We found that platelets of treated animals were not only hyper-responsive to thrombin and ADP, but also to sodium arachidonate. In addition, the results of the thrombin-induced release of labeled arachidonic acid pre-…

Synergistic interaction of adenylate cyclase activators and nitric oxide donor SIN-1 on platelet cyclic AMP

1995

Abstract The molecular mechanism of the synergistic platelet inhibition by activators of adenylate cyclase and guanylate cyclase in human platelets was investigated. The adenylate cyclase activators iloprost and prostaglandin E 1 and the guanylate cyclase activator 3-morpholino-synonimine (SIN-1) dose-dependently inhibited thrombin-induced aggregation of washed human platelets. Furthermore, SIN-1 at a concentration inhibiting platelet aggregation by only 10% shifted the IC 50 values of iloprost and prostaglandin E 1 by one order of magnitude to the left, indicating a synergistic action of adenylate cyclase and guanylate cyclase activators. Iloprost and prostaglandin E 1 dose-dependently ele…

A Neuroprotective Function for the Hematopoietic Protein Granulocyte-Macrophage Colony Stimulating Factor (GM-CSF)

2007

Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a hematopoietic cytokine responsible for the proliferation, differentiation, and maturation of cells of the myeloid lineage, which was cloned more than 20 years ago. Here we uncovered a novel function of GM-CSF in the central nervous system (CNS). We identified the GM-CSF α-receptor as an upregulated gene in a screen for ischemia-induced genes in the cortex. This receptor is broadly expressed on neurons throughout the brain together with its ligand and induced by ischemic insults. In primary cortical neurons and human neuroblastoma cells, GM-CSF counteracts programmed cell death and induces BCL-2 and BCL-Xl expression in a dose- a…

The CB1 cannabinoid receptor signals striatal neuroprotection via a PI3K/Akt/mTORC1/BDNF pathway

2015

The CB1 cannabinoid receptor, the main molecular target of endocannabinoids and cannabis active components, is the most abundant G protein-coupled receptor in the mammalian brain. In particular, the CB1 receptor is highly expressed in the basal ganglia, mostly on terminals of medium-sized spiny neurons, where it plays a key neuromodulatory function. The CB1 receptor also confers neuroprotection in various experimental models of striatal damage. However, the assessment of the physiological relevance and therapeutic potential of the CB1 receptor in basal ganglia-related diseases is hampered, at least in part, by the lack of knowledge of the precise mechanism of CB1 receptor neuroprotective ac…

Incidence of oncogenes in PI3K/AKT and MAPK signaling pathways in breast cancer

2015

CD44v6 is a marker of constitutive and reprogrammed cancer stem cells driving colon cancer metastasis.

2014

SummaryCancer stem cells drive tumor formation and metastasis, but how they acquire metastatic traits is not well understood. Here, we show that all colorectal cancer stem cells (CR-CSCs) express CD44v6, which is required for their migration and generation of metastatic tumors. CD44v6 expression is low in primary tumors but demarcated clonogenic CR-CSC populations. Cytokines hepatocyte growth factor (HGF), osteopontin (OPN), and stromal-derived factor 1α (SDF-1), secreted from tumor associated cells, increase CD44v6 expression in CR-CSCs by activating the Wnt/β-catenin pathway, which promotes migration and metastasis. CD44v6− progenitor cells do not give rise to metastatic lesions but, when…

Cyclic AMP-mediated upregulation of the expression of neuronal NO synthase in human A673 neuroepithelioma cells results in a decrease in the level of…

2004

The expression level of neuronal nitric oxide synthase (nNOS) can vary depending on the (patho)physiological conditions. Here we document a marked induction of nNOS mRNA, protein, and total NO production in response to dibutyryl cyclic AMP (db-cAMP) in human A673 neuroepithelial cells. However, the upregulation of nNOS was associated with a decreased level of production of bioactive NO and by an increase in the level of generation of reactive oxygen species (ROS). ROS production could be prevented by the NOS inhibitor L-NAME, suggesting nNOS itself is involved in ROS generation. Sepiapterin supplementation of db-cAMP-treated A673 cells could restore full bioactive NO production, most likely…

Rapamycin stimulates arginine influx through CAT2 transporters in human endothelial cells

2007

In endothelial cells Tumor Necrosis Factor-alpha (TNFalpha) stimulates arginine transport through the increased expression of SLC7A2/CAT2 transcripts. Here we show that also rapamycin, an inhibitor of mTOR kinase, stimulates system y(+)-mediated arginine uptake in human endothelial cells derived from either saphenous (HSVECs) or umbilical veins (HUVECs). When used together with TNFalpha, rapamycin produces an additive stimulation of arginine transport in both cell models. These effects are observed also upon incubation with AICAR, a stimulator of Adenosine-Monophosphate-dependent-Protein Kinase (AMPK) that produces a rapamycin-independent inhibition of the mTOR pathway. Rapamycin increases …

Reduced T-cell receptor CD3ζ-chain protein and sustained CD3ε expression at the site of mycobacterial infection

2001

Control of mycobacterial infection by the cellular immune system relies both on antigen-presenting cells and on T lymphocytes. The quality of an effective cellular immune response is dependent on functional signal transduction residing in the cytoplasmic tails of the T-cell receptor CD3 components. In order to investigate potential effects of mycobacteria on T-cell receptor signalling, we examined the protein expression of T-cell signal transduction molecules (CD3zeta, ZAP-70, p59fyn, p56lck). In Western blots of peripheral blood mononuclear cells of Mycobacterium tuberculosis infected patients, only the CD3zeta-chain showed a marked reduction in protein expression. To investigate the situa…

Impact of Glutathione Peroxidase-1 Deficiency on Macrophage Foam Cell Formation and Proliferation: Implications for Atherogenesis

2013

Clinical and experimental evidence suggests a protective role for the antioxidant enzyme glutathione peroxidase-1 (GPx-1) in the atherogenic process. GPx-1 deficiency accelerates atherosclerosis and increases lesion cellularity in ApoE(-/-) mice. However, the distribution of GPx-1 within the atherosclerotic lesion as well as the mechanisms leading to increased macrophage numbers in lesions is still unknown. Accordingly, the aims of the present study were (1) to analyze which cells express GPx-1 within atherosclerotic lesions and (2) to determine whether a lack of GPx-1 affects macrophage foam cell formation and cellular proliferation. Both in situ-hybridization and immunohistochemistry of l…