Search results for "Signal Transduction"
showing 10 items of 2020 documents
Physical exercise neuroprotects ovariectomized 3xTg-AD mice through BDNF mechanisms.
2014
Postmenopausal women may be more vulnerable to cognitive loss and Alzheimer's disease (AD) than premenopausal women because of their deficiency in estrogens, in addition to their usually older age. Aerobic physical exercise has been proposed as a therapeutic approach for maintaining health and well-being in postmenopausal women, and for improving brain health and plasticity in populations at high risk for AD. To study the neuroprotective mechanisms of physical exercise in a postmenopausal animal model, we submitted previously ovariectomized, six-month old non-transgenic and 3xTg-AD mice to three months of voluntary exercise in a running wheel. At nine months of age, we observed lower grip s…
Amphiregulin activates human hepatic stellate cells and is upregulated in non alcoholic steatohepatitis
2015
AbstractAmphiregulin (AR) involvement in liver fibrogenesis and hepatic stellate cells (HSC) regulation is under study. Non-alcoholic fatty liver disease (NAFLD) and its more severe form non-alcoholic steatohepatitis (NASH) may progress to cirrhosis and hepatocellular cancer (HCC). Our aim was to investigate ex vivo the effect of AR on human primary HSC (hHSC) and verify in vivo the relevance of AR in NAFLD fibrogenesis. hHSC isolated from healthy liver segments were analyzed for expression of AR and its activator, TNF-α converting enzyme (TACE). AR induction of hHSC proliferation and matrix production was estimated in the presence of antagonists. AR involvement in fibrogenesis was also ass…
Antiapoptotic effect of calcitonin gene-related peptide on oxidative stress-induced injury in H9c2 cardiomyocytes via the RAMP1/CRLR complex.
2005
Calcitonin gene-related peptide (CGRP) plays an important role in the mediation of protective effects observed in situations such as ischemic preconditioning in rat hearts. In this study, we investigated in H9c2 rat cardiomyoblasts if the protective effect of CGRP could be linked to an inhibitory effect on the apoptotic pathway. We also determined the specificity of observed effects by treatment with adrenomedullin (ADM) in stress conditions generated by 100 microM hydrogen peroxide. Using MTT assays, we demonstrate that a pretreatment with CGRP decreases by half the loss of cell viability induced by H(2)O(2). CGRP inhibits phosphatidylserine externalization, caspase 3 activation and DNA fr…
Hardwiring the Brain: Endocannabinoids Shape Neuronal Connectivity
2007
The roles of endocannabinoid signaling during central nervous system development are unknown. We report that CB 1 cannabinoid receptors (CB 1 Rs) are enriched in the axonal growth cones of γ-aminobutyric acid–containing (GABAergic) interneurons in the rodent cortex during late gestation. Endocannabinoids trigger CB 1 R internalization and elimination from filopodia and induce chemorepulsion and collapse of axonal growth cones of these GABAergic interneurons by activating RhoA. Similarly, endocannabinoids diminish the galvanotropism of Xenopus laevis spinal neurons. These findings, together with the impaired target selection of cortical GABAergic interneurons lacking CB 1 Rs, identify endoc…
Cyclic AMP-dependent and independent stimulations of ovarian steroidogenesis by brain factors in the blowfly, Phormia regina.
2000
0303-7207 doi: DOI: 10.1016/S0303-7207(00)00312-9; The involvement of cyclic-AMP (cAMP) as a potential second messenger in the neurohormonal control of ovarian steroidogenesis was investigated in the adult female blowfly Phormia regina. Individual measurements of ovarian cAMP concentrations and of ovarian biosynthesis of ecdysteroids, stimulated after a protein meal, demonstrated that steroidogenesis is preceded by a peak of cAMP in the ovaries. In vitro, ovarian steroidogenesis was stimulated by cell-permeable analogues of cAMP and by forskolin. Crude brain extracts were also able to elicit a rise of cAMP in the ovaries in vitro and the secretion of ecdysteroids into the medium: such extra…
Developmental programming of energy balance and its hypothalamic regulation.
2011
Developmental programming is an important physiological process that allows different phenotypes to originate from a single genotype. Through plasticity in early life, the developing organism can adopt a phenotype (within the limits of its genetic background) that is best suited to its expected environment. In humans, together with the relative irreversibility of the phenomenon, the low predictive value of the fetal environment for later conditions in affluent countries makes it a potential contributor to the obesity epidemic of recent decades. Here, we review the current evidence for developmental programming of energy balance. For a proper understanding of the subject, knowledge about ene…
Developmental and tumoral vascularization is regulated by G protein-coupled receptor kinase 2
2012
Tumor vessel dysfunction is a pivotal event in cancer progression. Using an in vivo neovascularization model, we identified G protein–coupled receptor kinase 2 (GRK2) as a key angiogenesis regulator. An impaired angiogenic response involving immature vessels was observed in mice hemizygous for Grk2 or in animals with endothelium-specific Grk2 silencing. ECs isolated from these animals displayed intrinsic alterations in migration, TGF-β signaling, and formation of tubular networks. Remarkably, an altered pattern of vessel growth and maturation was detected in postnatal retinas from endothelium-specific Grk2 knockout animals. Mouse embryos with systemic or endothelium-selective Grk2 ablation …
Diacylglycerol kinase α mediatses 17-β-estradiol-induced proliferation, motility, and anchorage-independent growth of Hec-1A endometrial cancer cell …
2011
Increased levels of endogenous and/or exogenous estrogens are one of the well known risk factors of endometrial cancer. Diacylglycerol kinases (DGKs) are a family of enzymes which phosphorylate diacylglycerol (DAG) to produce phosphatidic acid (PA), thus turning off and on DAG-mediated and PA-mediated signaling pathways, respectively. DGK α activity is stimulated by growth factors and oncogenes and is required for chemotactic, proliferative, and angiogenic signaling in vitro. Herein, using either specific siRNAs or the pharmacological inhibitor R59949, we demonstrate that DGK α activity is required for 17-β-estradiol (E2)-induced proliferation, motility, and anchorage-independent growth of …
Statin-Induced Liver Injury Involves Cross-Talk between Cholesterol and Selenoprotein Biosynthetic Pathways
2009
Statins have become the mainstay of hypercholesterolemia treatment. Despite a seemingly clear rationale behind their use, the inhibition of HMG-CoA reductase, these compounds have been shown to elicit a variety of unanticipated and elusive effects and side effects in vivo. Among the most frequently noted side effects of statin treatment are elevations in liver enzymes. Here, we report our finding that atorvastatin, cerivastatin, and lovastatin at clinically common concentrations induce a selective, differential loss of selenoprotein expression in cultured human HepG2 hepatocytes. The primarily affected selenoprotein was glutathione peroxidase (GPx), whose biosynthesis, steady-state expressi…
Inhibition of ovarian steroidogenesis by cyclic-GMP in a fly
2003
1479-6805 0022-0795; Previous investigations in the female blowfly Phormia regina have shown that 3-isobutyl-1-methylxanthine (IBMX), a broad spectrum inhibitor of phosphodiesterases (PDEs), fails to mimic the steroidogenic effects of cAMP on ovaries, although it efficiently increases the concentrations of this second messenger. In this study, experiments carried out to clear up this contradiction demonstrated that IBMX, besides its effect on cAMP, also increased cGMP concentrations in blowfly ovary and that these two cyclic nucleotides controlled ovarian steroidogenesis antagonistically. In particular, a selective inhibitor of cGMP-specific PDEs, unlike IBMX, had a very strong negative eff…