Search results for "nitric Oxide"
showing 10 items of 1075 documents
Protein kinase inhibitor-based cancer therapies: Considering the potential of nitric oxide (NO) to improve cancer treatment.
2020
The deregulation of a wide variety of protein kinases is associated with cancer cell initiation and tumor progression. Owing to their indispensable function in signaling pathways driving malignant cell features, protein kinases constitute major therapeutic targets in cancer. Over the past two decades, intense efforts in drug development have been dedicated to this field. The development of protein kinase inhibitors (PKIs) have been a real breakthrough in targeted cancer therapy. Despite obvious successes across patients with different types of cancer, the development of PKI resistance still prevails. Combination therapies are part of a comprehensive approach to address the problem of drug r…
Inactivation of the KSRP gene modifies collagen antibody induced arthritis.
2017
Abstract The KH type splicing regulatory protein (KSRP) is a nucleic acid binding protein, which negatively regulates the stability and/or translatability of many mRNA species encoding immune-relevant proteins. As KSRP is expressed in immune cells including T and B cells, neutrophils, macrophages and dendritic cells, we wanted to analyze its importance for the development of autoimmune diseases. We chose collagen antibody-induced arthritis (CAIA) as an appropriate autoimmune disease mouse model in which neutrophils and macrophages constitute the main effector cell populations. We compared arthritis induction in wild type (WT) and KSRP−/− mice and paws were taken for histological sections an…
Takotsubo Syndrome: Impact of endothelial dysfunction and oxidative stress
2021
Takotsubo Syndrome (TTS) is characterized by a transient left ventricular dysfunction recovering spontaneously within days or weeks. Although the pathophysiology of TTS remains obscure, there is growing evidence suggesting TTS to be associated with increased production of reactive oxygen species (ROS), which may be involved in causing transient coronary and peripheral endothelial dysfunction leading to a transient impairment of myocardial contraction due to stunning (apical ballooning). Endothelial dysfunction is mainly caused by decreased vascular and myocardial nitric oxide bioavailability in response to increased ROS production. Accordingly, studies in humans and animal models demonstrat…
Expression Pattern of Angiogenic Factors in Healthy Heart in Response to Physical Exercise Intensity
2019
Recently, many studies showing the regeneration potential of both cardiac and hematopoietic stem cells in adult heart following injury were definitively retracted by the literature. Therefore, stimulating myocardial angiogenesis becomes to be important for preventing cardiovascular diseases. Regular endurance exercise has been reported to induce capillary growth in healthy and diseased myocardium resulting in cardioprotective phenotype. Previously, we demonstrated a significantly increased capillary proliferation in mouse hearts following 30 and 45 days of endurance training. In the present study, we examined the localization and expression pattern of vascular endothelial growth factor rece…
Uncoupling of eNOS in Cardiovascular Disease
2017
Abstract Under physiological conditions, nitric oxide (NO) produced by the endothelial NO synthase (eNOS) represents a key vasoprotective factor. Under conditions of cardiovascular diseases, such as hypertension, diabetes, and atherosclerosis, eNOS may become uncoupled. Uncoupled eNOS generates superoxide at the expense of NO and contributes significantly to endothelial dysfunction and atherogenesis. Major mechanisms of eNOS uncoupling include depletion of tetrahydrobiopterin, an essential cofactor for the eNOS enzyme, and deficiency of l -arginine, the eNOS substrate, and/or eNOS S-glutathionylation. Reversal of eNOS uncoupling may represent a novel therapeutic strategy for the prevention …
Effects of resveratrol on eNOS in the endothelium and the perivascular adipose tissue
2017
Under physiological conditions, nitric oxide (NO) is produced in the vasculature mainly by the endothelial NO synthase (eNOS). Experiments using gene-disrupted mice have demonstrated that eNOS has antihypertensive, antithrombotic, and antiatherosclerotic effects. Recent studies show that eNOS is expressed not only in the endothelium but also in the perivascular adipose tissue (PVAT). Resveratrol prevents eNOS uncoupling and upregulates eNOS expression and activity. These effects of resveratrol are well established for the eNOS enzyme in the endothelium. Interestingly, resveratrol also improves PVAT function. However, a causal role for eNOS in the effects of resveratrol on PVAT function has …
Genetic inactivation of the sigma-1 chaperone protein results in decreased expression of the R2 subunit of the GABA-B receptor and increased suscepti…
2021
There is a growing body of evidence demonstrating the significant involvement of the sigma-1 chaperone protein in the modulation of seizures. Several sigma-1 receptor (Sig1R) ligands have been demonstrated to regulate the seizure threshold in acute and chronic seizure models. However, the mechanism by which Sig1R modulates the excitatory and inhibitory pathways in the brain has not been elucidated. The aim of this study was to compare the susceptibility to seizures of wild type (WT) and Sig1R knockout (Sig1R−/−) mice in intravenous pentylenetetrazol (PTZ) and (+)-bicuculline (BIC) infusion-induced acute seizure and Sig1R antagonist NE-100-induced seizure models. To determine pos…
Participation of Heme Oxygenase-1 in a Model of Acute Inflammation
2003
In this study, the role of heme oxygenase-1 (HO-1) in the inflammatory response elicited by zymosan in the mouse air pouch model has been examined. This response is characterized by a time-dependent increase in HO-1 expression in the leukocytes migrating into the exudates. At 24–48 h maximal HO-1 expression was accompanied by reduced cyclooxygenase-2 (COX-2) and nitric oxide synthase-2 (NOS-2) expression as well as low levels of inflammatory mediators. Hemin administration into the air pouch caused an elevation of HO-1 protein and bilirubin levels induced by zymosan with inhibition of COX-2 expression. In mouse peritoneal macrophages from hemin-injected mice, we also observed an increased …
Roles of Vascular Oxidative Stress and Nitric Oxide in the Pathogenesis of Atherosclerosis.
2017
Major reactive oxygen species (ROS)–producing systems in vascular wall include NADPH (reduced form of nicotinamide adenine dinucleotide phosphate) oxidase, xanthine oxidase, the mitochondrial electron transport chain, and uncoupled endothelial nitric oxide (NO) synthase. ROS at moderate concentrations have important signaling roles under physiological conditions. Excessive or sustained ROS production, however, when exceeding the available antioxidant defense systems, leads to oxidative stress. Animal studies have provided compelling evidence demonstrating the roles of vascular oxidative stress and NO in atherosclerosis. All established cardiovascular risk factors such as hypercholesterolemi…
Phosphodiesterase-5 Inhibition Alleviates Pulmonary Hypertension and Basal Lamina Thickening in Rats Challenged by Chronic Hypoxia
2018
javax.xml.bind.JAXBElement@6f8948ff Hypoxia represents both an outcome of cardiopulmonary diseases and a trigger for severe pulmonary complications as pulmonary hypertension. Because nitric oxide (NO) is a critical mediator in the development of pulmonary hypertension, the modulators of its downstream function may become target of pharmacological interventions aimed at alleviating the impact of this condition. Here, we investigate the effects of an early administration of phosphodiesterase-5 inhibitor in rats where pulmonary artery hypertension was induced by chronic exposure to hypoxia. javax.xml.bind.JAXBElement@162dc677 Rats were divided into three groups: normoxic control, hypoxic with …