1,721,079 research outputs found
Antitumoral effects of pharmacological ascorbate on gastric cancer cells: GLUT1 expression may not tell the whole story
Full text linkThe recently reported results of Lu et al. (Theranostics. 2018; 8: 1312-26) – highlighting GLUT1 expression as a marker for sensitivity of gastric cancer cells to therapeutic doses of ascorbate – are discussed in the light of additional factors potentially affecting the underlying processes, such as the concomitant expression of membrane gamma-glutamyltransferase activity, the resistance of cancer cells to oxidative injury and other known biomarkers
Cellular pathways for transport and efflux of ascorbate and dehydroascorbate
No full textThe mechanisms allowing the cellular transport of ascorbic acid represent a primary aspect for the understanding of the roles played by this vitamin in pathophysiology. Considerable research effort has been spent in the field, on several animal models and different cell types. Several mechanisms have been described to date, mediating the movements of different redox forms of ascorbic acid across cell membranes. Vitamin C can enter cells both in its reduced and oxidized form, ascorbic acid (AA) and dehydroascorbate (DHA), utilizing respectively sodium-dependent transporters (SVCT) or glucose transporters (GLUT). Modulation of SVCT expression and function has been described by cytokines, steroids and post-translational protein modification. Cellular uptake of DHA is followed by its intracellular reduction to AA by several enzymatic and non-enzymatic systems. Efflux of vitamin C has been also described in a number of cell types and different pathophysiological functions were proposed for this phenomenon, in dependence of the cell model studied. Cellular efflux of AA is mediated through volume-sensitive (VSOAC) and Ca(2+)-dependent anion channels, gap-junction hemichannels, exocytosis of secretory vesicles and possibly through homo- and hetero-exchange systems at the plasma membrane level. Altogether, available data suggest that cellular efflux of ascorbic acid - besides its uptake - should be taken into account when evaluating the cellular homeostasis and functions of this important vitamin
THE CHANGING FACES OF GLUTATHIONE, A CELLULAR PROTAGONIST.
Full text linkThe paper is an editorial introducing the research topic "The changing faces of glutathione, a cellular protagonist"
Protein S-cisteil-glicilazione mediata dall’attività gamma-glutamiltransferasica di membrana su proteine cellulari e dell’ambiente extracellulare
No full textIncreasing sputum levels of gamma-glutamyltransferase may identify cystic fibrosis patients who do not benefit from inhaled glutathione
No full textGlutathione (GSH) is decreased in cystic fibrosis (CF) airways, thus its resupply by inhalation has been employed to restore antioxidant defense. CF airways present however increased activity of gamma-glutamyltransferase (GGT), the enzyme specifically capable of degrading GSH, and thus inhaled GSH might be promptly catabolized. In addition, prooxidant reactions are known to originate during GGT-mediated GSH catabolism. We determined levels of GGT in the sputum samples obtained from a previously published trial of GSH inhalation treatment, and analyzed their correlations with inflammatory markers and FEV1% values. Results indicate that differentiating patients with increasing vs. decreasing GGT activity – as measured in sputum before and after the six months duration of the study – may discriminate subjects more likely profiting from inhaled GSH, as opposed to those with increasing GGT in which these treatments might even produce aggravation of the damage
Increasing levels of sputum gamma-glutamyltransferase may be a contraindication to glutathione inhalation therapies in cystic fibrosis
No full textGamma-glutamyltransferase of Cancer Cells at the Crossroads of Tumor Progression, Drug Resistance and Drug Targeting
No full textGamma-glutamyltransferase (GGT) is a key enzyme involved in glutathione metabolism and whose expression is often significantly increased in human malignancies. In the past years, several studies focused on the possible role of GGT in tumor progression, invasion and drug resistance. The involvement of a pro-oxidant activity of GGT, besides its early recognized contributions to cellular antioxidant defenses, has been repeatedly documented. GGT-derived pro-oxidants can modulate important redox-sensitive processes and functions of the cell, with particular reference to its proliferative/apoptotic balance, which has obvious and important implications in tumor progression and drug resistance. In addition, the specificity of the enzymatic reaction carried out by GGT suggests that suitable pro-drugs could be selectively metabolized (activated) by GGT expressed in tumor tissue. This paper is a review of the recent investigation in the field, focusing on the potential role of GGT as a diagnostic/prognostic marker, as well as a target for anticancer treatments
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