Search results for "Signal Transduction"
showing 10 items of 2020 documents
Characterization of sensory neurotransmission and its inhibition via alpha 2B-adrenoceptors and via non-alpha 2-receptors in rabbit iris.
1993
To find out whether, and which type of, adrenoceptors mediate prejunctional inhibition of sensory neurotransmitter release from trigeminal fibres, the modulation of twitch response to electrical field stimulation on rabbit isolated iris was investigated. Evoked iris sphincter contractions consisted of a minor fast cholinergic and a large slow component. The latter was unaffected by atropine and guanethidine, hence nonadrenergic noncholinergic in nature (NANC), but nearly completely abolished by capsaicin pretreatment and by the neurokinin receptor antagonist spantide. The response was probably not mediated by NK2 receptors as SR 48,968, an NK2 selective nonpeptide antagonist, failed to redu…
Regulation of the effects of CYP2E1-induced oxidative stress by JNK signaling
2014
The generation of excessive amounts of reactive oxygen species (ROS) leads to cellular oxidative stress that underlies a variety of forms of hepatocyte injury and death including that from alcohol. Although ROS can induce cell damage through direct effects on cellular macromolecules, the injurious effects of ROS are mediated largely through changes in signal transduction pathways such as the mitogen-activated protein kinase c-Jun N-terminal kinase (JNK). In response to alcohol, hepatocytes have increased levels of the enzyme cytochrome P450 2E1 (CYP2E1) which generates an oxidant stress that promotes the development of alcoholic steatosis and liver injury. These effects are mediated in larg…
Technical advance: Soluble OX40 molecule mimics regulatory T cell modulatory activity on FCεRI-dependent mast cell degranulation
2011
ABSTRACT Tregs play a central role in modulating FcɛRI-dependent MC effector functions in the course of the allergic response. Cellular interaction depends on the constitutive expression of OX40 on Tregs and the OX40L counterpart on MCs. Study of OX40L signaling on MCs is hampered by the need of a highly purified molecule, which triggers OX40L specifically. We now report that sOX40 mimics the physiological activity of Treg interaction by binding to activated MCs. When treated with sOX40, activated MCs showed decreased degranulation and Ca++ influx, whereas PLC-γ2 phosphorylation remained unaffected. Once injected into experimental animals, sOX40 not only located within the endothelium but a…
Cellular stress induces cap-independent alpha-enolase/MBP-1 translation.
2015
AbstractMyc promoter-binding protein-1 (MBP-1) is a shorter protein variant of the glycolytic enzyme alpha-enolase. Although several lines of evidence indicate that MBP-1 acts as a tumor suppressor, the cellular mechanisms and signaling pathways underlying MBP-1 expression still remain largely elusive. To dissect these pathways, we used the SkBr3 breast cancer cell line and non-tumorigenic HEK293T cells ectopically overexpressing alpha-enolase/MBP-1. Here, we demonstrate that induced cell stresses promote MBP-1 expression through the AKT/PERK/eIF2α signaling axis. Our results contribute to shedding light on the molecular mechanisms underlying MBP-1 expression in non-tumorigenic and cancer c…
Emerging contributions of formyl peptide receptors to neurodegenerative diseases.
2021
Abstract Inflammation is a central element of many neurodegenerative diseases. Formyl peptide receptors (FPRs) can trigger several receptor-dependent signal transduction pathways that play a key role in neuroinflammation and neurodegeneration. They are chemotactic receptors that help to regulate pro- and anti-inflammatory responses in most mammals. FPRs are primarily expressed in the immune and nervous systems where they interact with a complex pattern of pathogen-derived and host-endogenous molecules. Mounting evidence points towards a contribution of FPRs – via neuropathological ligands such as Amyloid beta, and neuroprotective ligands such as Humanin, Lipoxin A4, and Annexin A1 – to mult…
Endothelial Leptin Receptor Deletion Promotes Cardiac Autophagy and Angiogenesis Following Pressure Overload by Suppressing Akt/mTOR Signaling.
2019
Background: Cardiac remodeling is modulated by overnutrition or starvation. The adipokine leptin mediates energy balance between adipose tissue and brain. Leptin and its receptors are expressed in the heart. Methods and Results: To examine the importance of endothelial leptin signaling in cardiac hypertrophy, transverse aortic constriction was used in mice with inducible endothelium-specific deletion of leptin receptors (End.LepR-KO) or littermate controls (End.LepR-WT). End.LepR-KO was associated with improved left ventricular function (fractional shortening, 28.4% versus 18.8%; P =0.0114), reduced left ventricular dilation (end-systolic inner left ventricular diameter, 3.59 versus 4.08 m…
The lipoprotein receptor LRP1 modulates sphingosine-1-phosphate signaling and is essential for vascular development
2014
Low density lipoprotein receptor-related protein 1 (LRP1) is indispensable for embryonic development. Comparing different genetically engineered mouse models, we found that expression of Lrp1 is essential in the embryo proper. Loss of LRP1 leads to lethal vascular defects with lack of proper investment with mural cells of both large and small vessels. We further demonstrate that LRP1 modulates Gi-dependent sphingosine-1-phosphate (S1P) signaling and integrates S1P and PDGF-BB signaling pathways, which are both crucial for mural cell recruitment, via its intracellular domain. Loss of LRP1 leads to a lack of S1P-dependent inhibition of RAC1 and loss of constraint of PDGF-BB-induced cell migra…
The transmembrane receptor Uncoordinated5 (Unc5) is essential for heart lumen formation in Drosophila melanogaster
2011
AbstractTransport of liquids or gases in biological tubes is fundamental for many physiological processes. Our knowledge on how tubular organs are formed during organogenesis and tissue remodeling has increased dramatically during the last decade. Studies on different animal systems have helped to unravel some of the molecular mechanisms underlying tubulogenesis. Tube architecture varies dramatically in different organs and different species, ranging from tubes formed by several cells constituting the cross section, tubes formed by single cells wrapping an internal luminal space or tubes that are formed within a cell. Some tubes display branching whereas others remain linear without interse…
Angiogenic activity of breast cancer patients' monocytes reverted by combined use of systems modeling and experimental approaches.
2015
Angiogenesis plays a key role in tumor growth and cancer progression. TIE-2-expressing monocytes (TEM) have been reported to critically account for tumor vascularization and growth in mouse tumor experimental models, but the molecular basis of their pro-angiogenic activity are largely unknown. Moreover, differences in the pro-angiogenic activity between blood circulating and tumor infiltrated TEM in human patients has not been established to date, hindering the identification of specific targets for therapeutic intervention. In this work, we investigated these differences and the phenotypic reversal of breast tumor pro-angiogenic TEM to a weak pro-angiogenic phenotype by combining Boolean m…
Coagulation signaling and cancer immunotherapy.
2019
The last decades have delineated many interactions of the hemostatic system with cancer cells that are pivotal for cancer-associated thrombosis, angiogenesis and metastasis. Expanding evidence shows that platelets, the tissue factor pathway, and proteolytic signaling involving protease-activated receptors (PARs) are also central players in innate and adaptive immunity. Recent studies in immune-competent mice have uncovered new immune-evasive roles of coagulation signaling networks in the development and growth of different preclinical tumor models. Tumor-type specific PAR1 signaling facilitates the escape from immune surveillance by cytotoxic T cells. In addition, tumor-associated macrophag…