Search results for "ACTIVATOR"
showing 10 items of 488 documents
A non-canonical chemical feedback self-limits nitric oxide-cyclic GMP signaling in health and disease
2018
Endothelial nitric oxide (NO) stimulates the heme protein, soluble guanylyl cyclase (sGC) to form vasoprotective cyclic GMP (cGMP). In different disease states such as pulmonary hypertension, NO-cGMP signaling is pharmacologically augmented, yet the pathomechanisms leading to its dysregulation are incompletely understood. Here we show in pulmonary artery endothelial cells that endogenous NO or NO donor compounds acutely stimulate sGC activity, but chronically down-regulate both sGC protein and cGMP formation. Surprisingly, this endogenous feedback mechanism was independent of canonical cGMP signaling via cGMP-dependent protein kinase. It did not involve thiol-dependent modulation, a process…
Advancing stem cells: New therapeutic strategies for treating central nervous system disorders
2018
In this special issue, we explore new methods and knowledge to improve stem cell transplantation in diseases and conditions such as stroke, PD, and depression. Advancing the conventional idea regarding cell replacement in stem cell therapy, stem cells may also transfer healthy mitochondria to diseased ischemic neurons in stroke and improve the therapeutic time window of tissue plasminogen activator (tPA) in a conjunctive therapy for stroke, and human Wharton’s Jelly-derived mesenchymal stromal cells (hWJ-MSCs) may rely mainly on trophic factor secretion to induce neuroprotective effects. In addition, trophic factors such as neurotrophin-4/5 (NT-4/5) and glial cell line-derived neurotrophic …
Interleukin-15, as Interferon-gamma, Induces the Killing of Leishmania infantum in Phorbol-Myristate-Acetate-Activated Macrophages Increasing Interle…
2004
The potential leishmanicidal activity of interleukin-15 (IL-15) was examined while priming with the cytokine phorbol-myristate-acetate (PMA)-activated macrophages and infecting them with Leishmania infantum parasites. The activation of macrophage cultures with IL-15 determined a significant anti-leishmanial activity, comparable with that induced by interferon-gamma (IFN-gamma). The killing of Leishmania in macrophages primed with IL-15, as well as with IFN-gamma, was followed by an increase in the IL-12 synthesis. The neutralization of IL-15 or IFN-gamma, by specific monoclonal antibodies (MoAb) caused a significant reduction in leishmanicidal activity. Furthermore, in PMA-activated macroph…
Association of a single nucleotide polymorphism of RANK gene with blood pressure in Spanish women
2020
Abstract In addition to governing key functions in bone metabolism and the immune system, the RANK/RANKL/OPG system plays a role in the vascular system, particularly in vascular calcification and atherosclerosis. Given that these 2 phenotypes are considered a major cause of high blood pressure (BP), in this study we analyzed the association of SNPs in RANK and OPG genes with blood pressure. An observational study was conducted of 2 SNPs in the RANK gene (rs884205 and rs78326403) and 1 in the OPG gene (rs4876869) with systolic (SBP) and diastolic blood pressure (DBP) in a cohort of 695 women. Data analysis revealed a statistically significant association between the SNP rs884205 and BP press…
Human pasteurized C1-inhibitor concentrate for the treatment of hereditary angioedema due to C1-inhibitor deficiency.
2011
Hereditary angioedema is a relatively rare genetic disorder affecting between one in 10,000 and one in 50,000 individuals worldwide. The most common clinical symptoms observed are relapsing swelling of the skin and abdominal pain attacks. However, more serious and potentially fatal laryngeal attacks can also occur. Hereditary angioedema is most frequently caused by a deficiency of C1-inhibitor. Replacement therapy with Berinert, an intravenous pasteurized C1-inhibitor concentrate derived from human plasma, is a recommended treatment for rapid resolution of acute attacks of hereditary angioedema due to C1-inhibitor deficiency. Prophylactic therapy with C1-inhibitor is also available. Future …
Effects of soy isoflavones on endothelial function in healthy postmenopausal women.
2005
Objective: To evaluate the effects of soy isoflavone administration on endothelial function in healthy postmenopausal women. Design: Sixty naturally postmenopausal women were randomly assigned to receive isoflavone or placebo tablets for 6 months. Endothelium-dependent vasodilatation was measured by brachial reactivity technique along with levels of plasma soluble intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), E-selectin, P-selectin and soluble thrombomodulin, von Willebrand factor, and tissue plasminogen activator. Differences between endothelium-dependent and endothelium-independent vasodilatation were assessed by evaluating brachial reactivity par…
Different modes of activating phosphofructokinase, a key regulatory enzyme of glycolysis, in working vertebrate muscle
2002
Glycolytic flux in white muscle can be increased several-hundredfold by exercise. Phosphofructokinase (PFK; EC 2.7.1.11) is a key, regulatory enzyme of glycolysis, but how its activity in muscle is controlled is not fully, understood. In order not to neglect integrative aspects of metabolic regulation, we have studied in frogs (Rana temporaria) a physiological form of muscle work (swimming) that can be triggered like a reflex. We analysed swimming to fatigue in well rested frogs, recovery from exercise, and repeated exercise after 2 h of recovery. At various times, gastrocnemius muscles were tested for glycolytic intermediates and effectors of PFK. All metabolites responded similarly to the…
The estrogen receptor α:insulin receptor substrate 1 complex in breast cancer: structure–function relationships
2007
Background: Insulin receptor substrate 1 (IRS-1) is a signaling molecule that exerts a key role in mediating cross talk between estrogen receptor a (ERa) and insulin-like growth factor 1 (IGF-1) in breast cancer cells. Previously, we demonstrated that a fraction of IRS-1 binds ERa, translocates to the nucleus, and modulates ERa-dependent transcription at estrogen response elements (ERE). Here, we studied structure-function relationships of the ER-a:IRS-1 complex under IGF-1 and/or estradiol (E 2 ) stimulation. Materials and methods: ERa and IRS-1 deletion mutants were used to analyze structural and functional ERα/IRS-1 interactions. IRS-1 binding to ERE and IRS-1 role in ERa-dependent ERE t…
PGC-1α: a master gene that is hard to master
2012
Peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α) is a transcriptional coactivator that favorably affects mitochondrial function. This concept is supported by an increasing amount of data including studies in PGC-1α gene-deleted mice, suggesting that PGC-1α is a rescue factor capable of boosting cell metabolism and promoting cell survival. However, this view has now been called into question by a recent study showing that adeno-associated virus-mediated PGC-1α overexpression causes overt cell degeneration in dopaminergic neurons. How is this to be understood, and can these seemingly conflicting findings tell us something about the role of PGC-1α in cell stress and in cont…
Coronary thrombolysis with tissue-type plasminogen activator (t-PA)
1985
Coronary thrombolysis is presently under intensive investigation as a treatment for acute myocardial infarction for two main reasons. Firstly it is now well established that acute myocardial infarction is often associated with thrombotic occlusion of an atherosclerotic coronary artery [1]. Secondly it has been shown that administration of thrombolytic agents can reopen an occluded coronary artery in the majority of patients [2, 3] and that reperfusion of ischemic myocardial tissue is generally well tolerated. Coronary thrombolysis is however not a goal in itself but is employed to prevent necrosis and dysfunction of jeopardized myocardial cells. There is ample evidence in animals that the i…