Search results for "Pathway"
showing 10 items of 1685 documents
Thrombin generation in cardiovascular disease and mortality – results from the Gutenberg Health Study
2020
Thrombin generation may be a potential tool to improve risk stratification for cardiovascular diseases. The aim of this study was to explore the relation between thrombin generation and cardiovascular risk factors, cardiovascular diseases, and total mortality. For this study, 5,000 subjects from the population-based Gutenberg Health Study were analyzed in a highly standardized setting. Thrombin generation was assessed by the Calibrated Automated Thrombogram method at 1 and 5 pM tissue factor triggers in platelet-poor plasma. Lag time, endogenous thrombin potential, and peak height were derived from the thrombin generation curve. Sex-specific multivariable linear regression analysis adjusted…
Acute estradiol protects CA1 neurons from ischemia-induced apoptotic cell death via the PI3K/Akt pathway
2010
Global ischemia arising during cardiac arrest or cardiac surgery causes highly selective, delayed death of hippocampal CA1 neurons. Exogenous estradiol ameliorates global ischemia-induced neuronal death and cognitive impairment in male and female rodents. However, the molecular mechanisms by which a single acute injection of estradiol administered after the ischemic event intervenes in global ischemia-induced apoptotic cell death are unclear. Here we show that acute estradiol acts via the phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) signaling cascade to protect CA1 neurons in ovariectomized female rats. We demonstrate that global ischemia promotes early activation of glycogen syn…
Repression of Cyclic Adenosine Monophosphate Upregulation Disarms and Expands Human Regulatory T Cells
2011
Abstract The main molecular mechanism of human regulatory T cell (Treg)-mediated suppression has not been elucidated. We show in this study that cAMP represents a key regulator of human Treg function. Repression of cAMP production by inhibition of adenylate cyclase activity or augmentation of cAMP degradation through ectopic expression of a cAMP-degrading phosphodiesterase greatly reduces the suppressive activity of human Treg in vitro and in a humanized mouse model in vivo. Notably, cAMP repression additionally abrogates the anergic state of human Treg, accompanied by nuclear translocation of NFATc1 and induction of its short isoform NFATc1/αA. Treg expanded under cAMP repression, however,…
Modulation of hippocampal acetylcholine release after fimbria-fornix lesions and septal transplantation in rats
1997
Abstract Female Long–Evans rats sustained electrolytic lesions of the fimbria and the dorsal fornix causing a partial lesion of the septohippocampal pathway. Two weeks later, the rats received intra-hippocampal grafts of fetal septal cell suspensions. Nine to twelve months later, the release of acetylcholine (ACh) in the hippocampus of sham-operated, lesion-only and grafted rats was measured by microdialysis. The extent of cholinergic (re)innervation was determined by acetylcholinesterase (AChE) staining and densitometry. In both lesion-only and grafted rats, the ratio of ACh release to AChE staining intensity was increased as compared to sham-operated rats, indicating a loss of endogenous …
Newborn rabbit responsiveness to the mammary pheromone is concentration-dependent.
2004
The effect of the intensity of odour signals has rarely been investigated in the regulation of odour-guided behaviour in young mammals. This series of experiments used the mammary pheromone (MP) of the female rabbit to assess the influence of stimulus concentration on neonatal pup responsiveness. The MP is a single compound isolated from rabbit milk that releases in pups the typical head searching and oral seizing behaviour. The pups (n = 621) were exposed to graded concentrations of the MP in bioassays varying in stimulus delivery conditions. Experiment 1 demonstrated that in aqueous dilutions the MP efficiently elicits behavioural responses only within a limited range of concentrations (f…
Impact of serotonin 2C receptor null mutation on physiology and behavior associated with nigrostriatal dopamine pathway function.
2009
The impact of serotonergic neurotransmission on brain dopaminergic pathways has substantial relevance to many neuropsychiatric disorders. A particularly prominent role has been ascribed to the inhibitory effects of serotonin 2C receptor (5-HT2CR) activation on physiology and behavior mediated by the mesolimbic dopaminergic pathway, particularly in the terminal region of the nucleus accumbens. The influence of this receptor subtype on functions mediated by the nigrostriatal dopaminergic pathway is less clear. Here we report that a null mutation eliminating expression of 5-HT2CRs produces marked alterations in the activity and functional output of this pathway. 5-HT2CR mutant mice displayed i…
ANMCO/ISS/AMD/ANCE/ARCA/FADOI/GICR-IACPR/SICI-GISE/SIBioC/SIC/SICOA/SID/SIF/SIMEU/SIMG/SIMI/SISA Joint Consensus Document on cholesterol and cardiova…
2017
Atherosclerotic cardiovascular disease still represents the leading cause of death in western countries. A wealth of scientific evidence demonstrates that increased blood cholesterol levels have a major impact on the outbreak and progression of atherosclerotic plaques. Moreover, several cholesterol-lowering pharmacological agents, including statins and ezetimibe, have proven effective in improving clinical outcomes. This document is focused on the clinical management of hypercholesterolemia and has been conceived by 16 Italian medical associations with the support of the Italian National Institute of Health. The authors have considered with particular attention the role of hypercholesterole…
Growth and differentiation factor 11 (GDF11): Functions in the regulation of erythropoiesis and cardiac regeneration
2015
International audience; Members of the TGF-β superfamily transduce their signals through type I and II receptor serine/threonine kinases. The binding of activins to activin type IIA (ActRIIA) or type IIB (ActRIIB) receptors induces the recruitment and phosphorylation of an activin type I receptor (ALK4 and/or ALK7), which then phosphorylates the Smad2 and Smad3 intracellular signaling proteins. The regulation of members of the TGF-β family is known to be complex, because many proteins able to bind the ligands and inhibit their activities have been identified. Growth and differentiation factor 11 (Gdf11) belongs to the TGF-β family. GDF11, like other members of the TGF-β superfamily, is prod…
Control of ovarian steroidogenesis by insulin-like peptides in the blowfly (Phormia regina).
2004
0022–0795/04/0181–147; This study investigated the ability of insulin and of insect insulin-like peptides (ILPs) to stimulate ovarian steroidogenesis in the blowfly Phormia regina. Bovine insulin was active on ovaries isolated in vitro, which showed an age-dependent sensitivity; this peptide progressively stimulated steroidogenesis in ovaries isolated from the third day after adult molt, but not in younger ones, and had maximal activity after the fifth day. This stimulatory effect was observed equally from females reared in the presence or in the absence of males, excluding a regulatory effect of mating. The mode of action of insulin in blowflies did not involve cAMP, but triggered a specif…
Estradiol Stimulates Vasodilatory and Metabolic Pathways in Cultured Human Endothelial Cells
2009
Vascular effects of estradiol are being investigated because there are controversies among clinical and experimental studies. DNA microarrays were used to investigate global gene expression patterns in cultured human umbilical vein endothelial cells (HUVEC) exposed to 1 nmol/L estradiol for 24 hours. When compared to control, 187 genes were identified as differentially expressed with 1.9-fold change threshold. Supervised principal component analysis and hierarchical cluster analysis revealed the differences between control and estradiol-treated samples. Physiological concentrations of estradiol are sufficient to elicit significant changes in HUVEC gene expression. Notch signaling, actin cyt…