Abstract
Hyperglycemia is considered a threat for cell homeostasis, as it is associated to oxidative stress (OS). As erythrocytes are continuously exposed to OS, this study was conceived to verify the impact of either diabetic conditions attested to by glycated hemoglobin (Hb) levels (>6.5% or higher) or treatment with high glucose (15–35 mM, for 24 h) on erythrocyte homeostasis. To this aim, anion exchange capability through the Band 3 protein (B3p) was monitored by the rate constant for SO42− uptake. Thiobarbituric acid reactive species (TBARS), membrane sulfhydryl groups mostly belonging to B3p, glutathione reduced (GSH) levels, and B3p expression levels were also evaluated. The rate constant for SO42− uptake (0.063 ± 0.001 min−1, 16 min in healthy volunteers) was accelerated in erythrocytes from diabetic volunteers (0.113 ± 0.001 min−1, 9 min) and after exposure to high glucose (0.129 ± 0.001in−1, 7 min), but only in diabetic volunteers was there an increase in TBARS levels and oxidation of membrane sulfhydryl groups, and a decrease in both GSH and B3p expression levels was observed. A combined effect due to the glycated Hb and OS may explain what was observed in diabetic erythrocytes, while in in vitro hyperglycemia, early OS could explain B3p anion exchange capability alterations as proven by the use of melatonin. Finally, measurement of B3p anion exchange capability is a suitable tool to monitor the impact of hyperglycemia on erythrocytes homeostasis, being the first line of high glucose impact before Hb glycation. Melatonin may be useful to counteract hyperglycemia-induced OS at the B3p level.
Highlights
Diabetes mellitus type 2 (T2D) is a metabolic disease characterized by hyperglycemia, consisting of high glucose levels chronically present in the blood
1 shows the osmotic fragilityfragility in erythrocytes from both healthy (A) and diabetic (B), volunteers (B), reported as absorbance of hemoglobin released at different times of incubation reported as absorbance of hemoglobin released at different times of incubation (0–5–15–45–90–180 min)(0-5in min) in a 0.7%
After 24 h exposure to 15 or 35 mM glucose erythrocytes did not show Hb glycation (Figure 8); the alteration in anion exchange capability through Band 3 protein (B3p) could be ascribed to early oxidative damage rather than to autooxidation leading to glycation of proteins, as shown by the abovementioned studies [42,58]
Summary
Diabetes mellitus type 2 (T2D) is a metabolic disease characterized by hyperglycemia, consisting of high glucose levels chronically present in the blood. About 10.3% of the adult population in Europe is estimated to have diabetes, and, as expected, this percentage is going to increase substantially by 2030 due to the fact of obesity and aging [2]. Oxidative stress (OS) is critically involved in diabetes pathogenesis [3] and hyperglycemia is the principal factor in the early stages of development [4]. Hyperglycemic complications, such as glycosylated proteins formation [5], increase reactive oxygen species (ROS) generation, decrease nitric oxide (NO) production, and activation of the protein kinase C (PKC) and polyol pathways may contribute to OS [6].
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