Abstract
d-Galactose (d-Gal), when abnormally accumulated in the plasma, results in oxidative stress production, and may alter the homeostasis of erythrocytes, which are particularly exposed to oxidants driven by the blood stream. In the present investigation, the effect of d-Gal (0.1 and 10 mM, for 3 and 24 h incubation), known to induce oxidative stress, has been assayed on human erythrocytes by determining the rate constant of SO42− uptake through the anion exchanger Band 3 protein (B3p), essential to erythrocytes homeostasis. Moreover, lipid peroxidation, membrane sulfhydryl groups oxidation, glycated hemoglobin (% A1c), methemoglobin levels (% MetHb), and expression levels of B3p have been verified. Our results show that d-Gal reduces anion exchange capability of B3p, involving neither lipid peroxidation, nor oxidation of sulfhydryl membrane groups, nor MetHb formation, nor altered expression levels of B3p. d-Gal-induced %A1c, known to crosslink with B3p, could be responsible for rate of anion exchange alteration. The present findings confirm that erythrocytes are a suitable model to study the impact of high sugar concentrations on cell homeostasis; show the first in vitro effect of d-Gal on B3p, contributing to the understanding of mechanisms underlying an in vitro model of aging; demonstrate that the first impact of d-Gal on B3p is mediated by early Hb glycation, rather than by oxidative stress, which may be involved on a later stage, possibly adding more knowledge about the consequences of d-Gal accumulation.
Highlights
Introduction dGalactose (d-Gal) is a monosaccharide sugar, whose metabolism is connected to glucose metabolism [1]
After pretreatment of erythrocytes with 50 mM 3-AT and subsequent treatment with d-Gal, the rate constant of SO4 2− uptake was significantly lower than both control and d-Gal (0.1 or 10 mM) treatment (0.065 ± 0.001 min−1, ***,§§§, p < 0.001; 0.066 ± 0.001 min−1, ***, p < 0.001 and 0.040 ± 0.001 min−1, ns, ***, p < 0.001; 0.038 ± 0.001 min−1, ***, p < 0.001, §, p < 0.05; Table 1)
Though several in vivo experiments have been conducted on plasma or blood cells from animal models [6,18,19,20,21], the action mechanism of excessive d-Gal on human erythrocytes remains poorly clarified. d-Galactose-induced superoxide production implies H2 O2 formation due to superoxide dismutase (SOD)
Summary
Introduction dGalactose (d-Gal) is a monosaccharide sugar, whose metabolism is connected to glucose metabolism [1]. It is rapidly metabolized to glucose through specific enzymes and driven from peripheral blood to glycolysis pathway to give energy to the cell [2], keeping plasma d-Gal levels very low The overproduction of oxidative stress is a common patho-physiological state underlying many chronic diseases, such as cardiovascular diseases [12,13], neurodegenerative diseases [14], cancer [15], metabolic disorders (diabetes mellitus [16]), and diseases related to aging [17], the precise mechanisms contributing to the oxidative stress-induced damage are still under investigation. Several studies have exploited the in vivo exposure to d-Gal as a typical model for exploring the mechanisms underlying oxidative stress-related diseases in plasma or blood cells [6,18,19,20,21]. The effects of d-Gal on oxidative stress production in human erythrocytes have been only partially clarified [22]
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