1,721,036 research outputs found
Nongenomic actions of thyroid hormones: focus on membrane transport systems.
No full textExtranuclear or nongenomic effects of thyroid hormones are unaffected by inhibitors of protein synthesis, and their rapid time course cannot be explained by interaction of the hormone molecule with nuclear receptors. Their origin has been localized at the plasma membrane, but also at organelles such as the endoplasmatic reticulum and mitochondria. Thyroid hormone has been reported to activate, by both genomic and non genomic mechanisms, the Ca2+-ATPase that stores calcium from the cytosol in the sarcoplasmic reticulum; the decrease in intracellular Ca2+ leads to muscle relaxation. Considering the important effects on the cardiovascular system, T3 can actually be envisaged as a potent inotropic drug. T3 is also a major regulator of the plasma membrane Na+/K+-ATPase activity; T3 and its analog 3,5-diiodothyronine rapidly inhibits Na+/K+-ATPase in chick embryo hepatocytes, whereas the activity is up-regulated in alveolar epithelial cells. Also the ubiquitous plasma membrane Na+/H+ exchanger, that regulates cell volume and pH by exchanging extracellular Na+ with cytoplasmic H+ according to the concentration gradient, is activated by T3 via both genomic and nongenomic mechanisms. A growing number of natural and synthetic thyroid hormone analogs are available to study the physiological importance of extranuclear effects; this may lead to compounds that selectively target either genomic or nongenomic receptors. Such drugs may make it possible to activate separately only a part of the complex effects normally induced by thyroid hormones, this could be of clinical relevance for the cardiovascular system, bone tissue and the Central Nervous System
3,5,3-triiodothyronine (T3) stimulates cell growth through reactive oxigen species (ROS) and PI3K/AKT pathway
No full textEffect of Fructose and 3,5-Diiodothyronine (3,5-T2) on Lipid Accumulation and Insulin Signalling in Non-Alcoholic Fatty Liver Disease (NAFLD)-Like Rat Primary Hepatocytes
No full textNon-alcoholic fatty liver disease (NAFLD) is nowadays considered as one of the most serious pathological conditions affecting the liver. NAFLD is supposed to be initiated by the accumulation of lipids in the liver, which finally results in an impaired hepatic insulin signalling. Many researchers have recently focused their attention on the role played by fructose as a NAFLD-triggering agent, because of the increased diffusion of fructose-sweetened food. However, epidemiological data do not permit to evaluate the role of fructose per se, because these foods are often associated with elevated energy intake and unhealthy lifestyle. In the present work, we analysed the effects of fructose on the accumulation of lipids and insulin signalling in rat primary hepatocytes. Moreover, we investigated the effect of the thyroid hormone metabolite, devoid of thyrotoxic effects, 3,5-diiodothyronine (3,5-T 2) over the same parameters. To evaluate the effect on insulin signalling we took into consideration three key proteins, such as p85 subunit of phosphatidylinositol 3-kinase (PI3K), phosphatase and tensin homolog (PTEN), and Akt. Our results show that fructose in vitro, in the range of physiological concentrations, was not able to stimulate either lipid accumulation or to impair insulin signalling in our NAFLD-like rat primary hepatocytes. Our data thus support the idea that fructose per se may exert detrimental effects mainly triggering systemic effects, rather than directly affecting isolated hepatocytes. Moreover, we demonstrated that 3,5-T2, at physiological levels, reduces lipid content and triggers phosphorylation of Akt in an insulin receptor-independent manner, revealing new interesting properties as a biologically active molecule.©Georg Thieme Verlag KG Stuttgart. New York
Atrial natriuretic peptide and oxidative stress
No full textAtrial natriuretic peptide (ANP) is a hormone, produced mainly by cardiomyocytes, with a major role in cardiovascular homeostatic mechanisms such as natriuresis and vasodilation, which serve to regulate blood pressure. However, ANP also acts as an autocrine/paracrine factor on other targets such as kidney, lung, thymus, liver and the immune system. ANP participates in the regulation of cell growth and proliferation, and evidence is accumulating that these effects are associated with the generation of reactive oxygen species (ROS). In vascular cells and cardiomyocytes ANP stimulates the antioxidant defense, but in other systems such as hepatoblastoma and macrophages ANP may produce either antioxidant or prooxidant effects, depending on experimental conditions and cell context. At present very little is known on the relationship between ANP and ROS production in the normal homeostatic processes or during the development of cardiovascular diseases and cancer. Our current knowledge of the role of ANP in signaling pathways leading to the generation of intracellular messengers such as diacylglycerol (DAG), and guanosine 3'-5'-cyclic monophosphate has been examined in order to clarify the mechanisms by which the hormone may counteract or contribute to the potentially dangerous effects of free radicals
Computational studies reveal mechanism by which quinone derivatives can inhibit SARS-CoV-2. Study of embelin and two therapeutic compounds of interest, methyl prednisolone and dexamethasone.
No full textProliferative non genomic effects of thyroid hormines are mediated by PI3Kinase/AKT activation and ROS production
No full textInvolvement of plasma membrane redox systems in hormone action.
No full textReactive oxygen species (ROS) is the common name used to describe the partially reduced forms of molecular oxygen that may be generated in cells during oxidative metabolism. They are normally considered to be toxic, and cells possess various defence systems to protect themselves including antioxidant enzymes and low molecular weight antioxidants like vitamin C and vitamin E. However, it is now clear that small amounts of ROS also act as messenger molecules in cell signal transduction pathways; the plasma membrane of eukaryotic cells in particular contains a variety of different ROS-producing oxidases and reductases, of which the best characterized are the superoxide-producing NADPH oxidases. It has been known for many years that membrane redox activity can be changed rapidly by various hormones and growth factors, but the molecular mechanisms involved and the physiological importance of this phenomenon have only recently begun to be unveiled. This review summarizes the state of the art on plasma membrane-based ROS signalling in the pathways of insulin, steroid and thyroid hormones and growth factors. The apparent paradox of ROS being essential biomolecules in the regulation of cellular functions, but also toxic by-products of metabolism, may be important for the pharmacological application of natural and synthetic antioxidants
3-Hydroxy-3-methylglutaryl coenzyme A reductase regulation by antioxidant compounds: new therapeutic tools for hypercholesterolemia?
No full textOxidative stress has recently been implicated in the pathogenesis of various diseases such as diabetes and coronary artery disease whose main modifiable risk factor is the abnormal level of lipids and/or lipoproteins in the blood. Thus, the maintenance of cholesterol homeostasis together with the reduction of intracellular reactive oxygen species content could partially prevent the occurrence of atherosclerotic phenomena. Owing to the ability exerted by some antioxidants to modulate the activity and/or the protein levels of 3-hydroxy-3-methylglutaryl coenzyme A reductase (the rate-limiting enzyme of cholesterol biosynthetic pathway), their use as additional approach to the management of hypercholesterolemia should be taken into account. Here we provide an up-dated overview of the antioxidants whose ability to affect 3-hydroxy-3-methylglutaryl coenzyme A reductase either in the short- or in the long-term regulations has been reported
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