1,721,059 research outputs found
Glutamine Synthetase: Localization Dictates Outcome
Full text linkGlutamine synthetase (GS) is the adenosine triphosphate (ATP)-dependent enzyme that catalyses the synthesis of glutamine by condensing ammonium to glutamate. In the circulatory system, glutamine carries ammonia from muscle and brain to the kidney and liver. In brain reduction of GS activity has been suggested as a mechanism mediating neurotoxicity in neurodegenerative disorders. In cancer, the delicate balance between glutamine synthesis and catabolism is a critical event. In vitro evidence, confirmed in vivo in some cases, suggests that reduced GS activity in cancer cells associates with a more invasive and aggressive phenotype. However, GS is known to be highly expressed in cells of the tumor microenvironment, such as fibroblasts, adipocytes and immune cells, and their ability to synthesize glutamine is responsible for the acquisition of protumoral phenotypes. This has opened a new window into the complex scenario of the tumor microenvironment, in which the balance of glutamine consumption versus glutamine synthesis influences cellular function. Since GS expression responds to glutamine starvation, a lower glutamine synthesizing power due to the absence of GS in cancer cells might apply a metabolic pressure on stromal cells. This event might push stroma towards a GS-high/protumoral phenotype. When referred to stromal cells, GS expression might acquire a 'bad' significance to the point that GS inhibition might be considered a conceivable strategy against cancer metastasis
Editorial: Understanding how myeloid cell development and function meet tissue distinct metabolic requirements
Full text linkElements in support of the 'non-identity' of the PGRMC1 protein with the σ2 receptor
Full text linkσ2 Receptor subtype is overexpressed in a variety of human tumors, with σ2 agonists showing antiproliferative effects towards tumor cells through multiple pathways that depend both on the tumor cell type and on the molecule type. Therefore, σ2 receptor is an intriguing target for tumor diagnosis and treatment despite the fact that that it has not yet been cloned. One of the last attempts to characterize σ2 receptors led to identify it as the progesterone receptor membrane component 1 (PGRMC1). Although still controversial, such identity appears to have been accepted. We the aim of contributing to solve this controversy, in this work we stably silenced or overexpressed PGRMC1 protein in human MCF7 adenocarcinoma cells. Western blotting analyses were performed to quantify the presence of PGRMC1 protein on each of the three MCF7 cell lines variants, while scatchard analyses with radioligand were performed in order to determine the expression of the σ2 receptors. In order to correlate the antiproliferative effect of σ2 receptor agonist with PGRMC1 density, some σ2 ligands were administered to each of the three MCF7 cells variants. The results suggested that PGRMC1 and σ2 receptors are two different molecular entities
“Pharmacological Targeting of Glutamine Synthetase Skews Macrophages Toward An Inflammatory Phenotype and Inhibits Metastasis”
No full textPharmacological Targeting of Glutamine Synthetase Skews Macrophages Toward An Inflammatory Phenotype and Inhibits Metastasi
ATP-citrate lyase is essential for macrophage inflammatory response
No full textGrowing evidence suggests that energy metabolism and inflammation are closely linked and that cross-talk between these processes is fundamental to the pathogenesis of many human diseases. However, the molecular mechanisms underlying these observations are still poorly understood. Here we describe the key role of ATP-citrate lyase (ACLY) in inflammation. We find that ACLY mRNA and protein levels markedly and quickly increase in activated macrophages. Importantly, ACLY activity inhibition as well as ACLY gene silencing lead to reduced nitric oxide, reactive oxygen species and prostaglandin E2 inflammatory mediators. In conclusion, we present a direct role for ACLY in macrophage inflammatory metabolism. © 2013 Elsevier Inc
Elements in support of the 'non-identity' of the PGRMC1 protein with the σ2 receptor
No full textσ2 Receptor subtype is overexpressed in a variety of human tumors, with σ2 agonists showing antiproliferative effects towards tumor cells through multiple pathways that depend both on the tumor cell type and on the molecule type. Therefore, σ2 receptor is an intriguing target for tumor diagnosis and treatment despite the fact that that it has not yet been cloned. One of the last attempts to characterize σ2 receptors led to identify it as the progesterone receptor membrane component 1 (PGRMC1). Although still controversial, such identity appears to have been accepted. We the aim of contributing to solve this controversy, in this work we stably silenced or overexpressed PGRMC1 protein in human MCF7 adenocarcinoma cells. Western blotting analyses were performed to quantify the presence of PGRMC1 protein on each of the three MCF7 cell lines variants, while scatchard analyses with radioligand were performed in order to determine the expression of the σ2 receptors. In order to correlate the antiproliferative effect of σ2 receptor agonist with PGRMC1 density, some σ2 ligands were administered to each of the three MCF7 cells variants. The results suggested that PGRMC1 and σ2 receptors are two different molecular entities
inibitori del carrier del citrato nel trattamento dell'infiammazione
No full textLa presente invenzione riguarda l’acido 4-cloro-3-{[(3-nitrofenil)amino]sulfonil} benzoico (CNFASB), uno specifico inibitore del carrier mitocondriale del citrato (CIC). Il carrier del citrato (CIC), catalizza lo scambio elettroneutro tra citrato (H-citrato2-) e la forma non protonata del malato (malato2-). Il citrato esportato dai mitocondri verso il citosol, mediante il CIC, è scisso dall’ATP-citrato liasi (CL) in ossalacetato e acetilCoA che porterà alla biosintesi di steroli e acidi grassi. L’acetilCoA è necessario per l’allungamento degli acidi grassi polinsaturi che riformeranno l’acido arachidonico utilizzato nella biosintesi delle prostaglandine durante il processo infiammatorio. L’ossalacetato prodotto nel citosol dalla CL è ridotto a malato, e quest’ultimo, a sua volta, convertito in piruvato da parte dell’enzima malico con conseguente produzione, nel citosol, di NADPH+\H+ necessario per la sintesi di steroli e acidi grassi ma anche per l’attività dell’enzima ossido nitrico sintetasi inducibile (iNOS) che produrrà NO e per l’attività della NADPH ossidasi che produrrà i ROS
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