Abstract
Glucose autoxidation has been proposed as a key reaction associated with deleterious effects induced by hyperglycemia in the eye lens. Little is known about chromophores generated during glucose autoxidation. In this study, we analyzed the effect of oxidative and dicarbonyl stress in the generation of a major chromophore arising from glucose degradation (GDC) and its association with oxidative damage in lens proteins. Glucose (5 mM) was incubated with H2O2 (0.5–5 mM), Cu2+ (5–50 μM), glyoxal (0.5–5 mM) or methylglyoxal (0.5–5 mM) at pH 7.4, 5% O2, 37 °C, from 0 to 30 days. GDC concentration increased with incubation time, as well as when incubated in the presence of H2O2 and/or Cu2+, which were effective even at the lowest concentrations. Dicarbonylic compounds did not increase the levels of GDC during incubations. 1H, 13C and FT-IR spectra from the purified fraction containing the chromophore (detected by UV/vis spectroscopy) showed oxidation products of glucose, including gluconic acid. Lens proteins solutions (10 mg/mL) incubated with glucose (30 mM) presented increased levels of carboxymethyl-lysine and hydrogen peroxide that were associated with GDC increase. Our results suggest a possible use of GDC as a marker of autoxidative reactions occurring during lens proteins glycation induced by glucose.
Highlights
Sustained hyperglycemia states constitute a risk factor for the development of numerous non-communicable chronic diseases, including cataract disease [1]
The effect of oxidative stress in the generation of the major chromophore arising from glucose
Non-enzymatic reactions mediated by glucose have been proposed to play an important role in the etiology of nuclear cataract disease [16]
Summary
Sustained hyperglycemia states constitute a risk factor for the development of numerous non-communicable chronic diseases, including cataract disease [1]. Hyperglycemia (states) has been associated with the generation of advanced glycation end products (AGEs), which in crystallins proteins of the human eye lens have been shown to increase during aging and in nuclear cataract disease [2]. Glucose autoxidation has been proposed as an important pathway to generate reactive dicarbonyl compounds and AGEs during protein glycation [3]. The analysis of incubations performed in vitro with glucose and lysozyme or RGD-α3NC1domain of collagen 1 has shown that the glucose autoxidation products, glyoxal and methylglyoxal, were responsible for inhibiting the enzymatic and receptor–ligand interaction, respectively [4]. Ex vivo analysis of AGEs in eye lens proteins from human
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