Search results for "HOMEOSTASIS"
showing 10 items of 630 documents
The Use of Hepatocytes to Investigate Drug Toxicity
2010
The liver is very active in metabolizing foreign compounds and the major target for toxicity caused by drugs. Hepatotoxicity may be the result of the drug itself or, more frequently, a result of the bioactivation process and the production of reactive metabolites. Prioritization of compounds based on human hepatotoxicity potential is currently a key unmet need in drug discovery, as it can become a major problem for several lead compounds in later stages of the drug discovery pipeline. Therefore, evaluation of potential hepatotoxicity represents a critical step in the development of new drugs. Cultured hepatocytes are increasingly used by the pharmaceutical industry for the screening of hepa…
Fungal genes related to calcium homeostasis and signalling are upregulated in symbiotic arbuscular mycorrhiza interactions
2012
Fluctuations in intracellular calcium levels generate signalling events and regulate different cellular processes. Whilst the implication of Ca2+ in plant responses during arbuscular mycorrhiza (AM) interactions is well documented, nothing is known about the regulation or role of this secondary messenger in the fungal symbiont. The spatio-temporal expression pattern of putatively Ca2+-related genes of Glomus intraradices BEG141 encoding five proteins involved in membrane transport and one nuclear protein kinase, was investigated during the AM symbiosis. Expression profiles related to successful colonization of host roots were observed in interactions of G. intraradices with roots of wild-ty…
New therapeutic strategies for treatment of inflammatory bowel disease
2008
Although the precise etiology of inflammatory bowel disease (IBD) still remains unclear, considerable progress has been made in the identification of cytokine-mediated signaling pathways involved in the inflammatory process. Recent data have clearly shown that these pathways induce augmented intestinal T-cell activation and thus resistance to apoptosis, which is a central process in disease pathogenesis, as it impairs mucosal homeostasis. Therefore, novel therapeutic strategies aim at restoring activated effector T-cell susceptibility to apoptosis in the gut, based on a pathophysiological rationale. This development is best exemplified by the emergence of agents that target the TNF pathway,…
Persistent inflammation alters the function of the endogenous brain stem cell compartment
2008
Endogenous neural stem/precursor cells (NPCs) are considered a functional reservoir for promoting tissue homeostasis and repair after injury, therefore regenerative strategies that mobilize these cells have recently been proposed. Despite evidence of increased neurogenesis upon acute inflammatory insults (e.g. ischaemic stroke), the plasticity of the endogenous brain stem cell compartment in chronic CNS inflammatory disorders remains poorly characterized. Here we show that persistent brain inflammation, induced by immune cells targeting myelin, extensively alters the proliferative and migratory properties of subventricular zone (SVZ)-resident NPCs in vivo leading to significant accumulation…
Trace elements in glucometabolic disorders: an update.
2010
International audience; Many trace elements, among which metals, are indispensable for proper functioning of a myriad of biochemical reactions, more particularly as enzyme cofactors. This is particularly true for the vast set of processes involved in regulation of glucose homeostasis, being it in glucose metabolism itself or in hormonal control, especially insulin. The role and importance of trace elements such as chromium, zinc, selenium, lithium and vanadium are much less evident and subjected to chronic debate. This review updates our actual knowledge concerning these five trace elements. A careful survey of the literature shows that while theoretical postulates from some key roles of th…
Flavonoids in Bone Erosive Diseases: Perspectives in Osteoporosis Treatment
2020
Imbalance of bone homeostasis, with excessive bone resorption compared with bone formation, leads to the development of progressive osteopenia leading to lower bone resistance to load, with consequent pain and functional limitations. Phytochemicals with therapeutic and preventive effects against bone resorption have recently received increasing attention since they are potentially more suitable for long-term use than traditional therapeutic chemical compounds. In this systematic review of the literature of the past 5 years, comprehensive information is provided on flavonoids with potential antiresorption and pro-osteogenic effects. It aims to highlight the molecular mechanisms of these mole…
Astrocytes of the murine model for Down Syndrome Ts65Dn display reduced intracellular ionic zinc.
2014
Zinc is an essential trace element that is critical for a large number of structural proteins, enzymatic processes and transcription factors. In the brain, zinc ions are involved in synaptic transmission. The homeostasis of zinc is crucial for cell survival and function, and cells have developed a wide variety of systems to control zinc concentration. Alterations in free zinc concentration have been related with brain dysfunction. Down Syndrome individuals present alterations in free zinc concentration and in some of the proteins related with zinc homeostasis. We have analyzed the amount of free zinc and the zinc chelating protein metallothionein 3 in the astrocytes using primary cultures o…
Ethanol reduces zincosome formation in cultured astrocytes.
2010
Aims Zinc is an ion that participates in basic cellular and tissular functions. Zinc deficiency is present in many physiological and health problems affecting most body organs, including the brain. Among the circumstances involved in zinc deficiency, ethanol consumption is probably one of the most frequent. A dietary zinc supplement has been proposed as possibly being an efficient method to palliate zinc deficiency. Astrocytes form part of the hematoencephalic barrier, and they are apparently implicated in the homeostasis of the neuronal medium. In this work, we analyze the effect of ethanol on extracellular zinc management by rat astrocytes in culture. Methods Intracellular levels of 'free…
Hypothalamic glucose sensing : mitochondrial dynamic involument in reactive oxygen species signaling
2011
Energetic homeostasis results in the balance between energy intake and expenditure. The hypothalamus plays an important role in the regulation of both energetic metabolism and food intake in sensing hormonal and metabolic signals. For instance, changes in hypothalamic glucose level modulate food intake and insulin secretion. We have previously found that 1) increased hypothalamic glucose level triggers production of mitochondrial reactive oxygen species (mROS) from the electron transport chain; 2) hypothalamic mROS production is involved in glucose homeostasis and food intake control. The molecular mechanisms involved in glucose-induced hypothalamic mROS production are still unknown. Mitoch…
CLA-Enriched Diet Containing t10,c12-CLA Alters Bile Acid Homeostasis and Increases the Risk of Cholelithiasis in Mice
2011
International audience; Mice fed a mixture of CLA containing t10,c12-CLA lose fat mass and develop hyperinsulinemia and hepatic steatosis due to an accumulation of TG and cholesterol. Because cholesterol is the precursor in bile acid (BA) synthesis, we investigated whether t10,c12-CLA alters BA metabolism. In Expt. 1, female C57Bl/6J mice were fed a standard diet for 28 d supplemented with a CLA mixture (1 g/100 g) or not (controls). In Expt. 2, the feeding period was reduced to 4, 6, and 10 d. In Expt. 3, mice were fed a diet supplemented with linoleic acid, c9,t11-CLA, or t10,c12-CLA (0.4 g/100 g) for 28 d. In Expt. 1, the BA pool size was greater in CLA-fed mice than in controls and the …