Abstract
Glycative stress influences tumor progression. The aim of the present study was to evaluate the advanced glycation end products/soluble receptor of advanced glycation end products (AGE/sRAGE) axis in patients with multiple myeloma (MM). Blood samples were taken from 19 patients affected by MM and from 16 sex-matched and age-matched healthy subjects. AGE and sRAGE axis were dosed in patients with MM and matched with controls. AGEs were measured by spectrofluorimetric methods. Blood samples for the determination of sRAGE were analyzed by ELISA. AGE levels were significantly reduced in patients with respect to controls. Instead, sRAGE was significantly elevated in patients affected by MM compared to healthy subjects. Moreover, we showed that there was a statistically significant difference in sRAGE according to the heavy and light chain. IgA lambda had significantly higher sRAGE values than IgA kappa, IgG kappa, and IgG Lambda MM patients. From our data emerges the role of the sRAGE/AGE axis in MM. Since AGE is a positive regulator of the activity of RAGE, circulating sRAGE concentrations may reflect RAGE expression and may be raised in parallel with serum AGE concentrations as a counter-system against AGE-caused tissue damage. Serum concentrations of AGE and sRAGE could therefore become potential therapeutic targets.
Highlights
Glycation is a common reaction that happens in most cells between a carbonyl group (–C=O) of the reducing sugars and the amino group (–NH2) of proteins, initially leading to the creation of an unstable substance known as Schiff’s base
We evaluated the plasma concentrations of advanced oxidation protein products (AOPPs) and protein nitrosylation in order to measure the oxidative stress in untreated MM subjects and in subjects affected by monoclonal gammopathy of uncertain significance (MGUS) [18]
We demonstrated that plasma levels of AOPPs and S-nitrosylated proteins were considerably augmented in MM subject with respect to controls and to MGUS subjects
Summary
Glycation is a common reaction that happens in most cells between a carbonyl group (–C=O) of the reducing sugars and the amino group (–NH2) of proteins, initially leading to the creation of an unstable substance known as Schiff’s base. Schiff’s bases are short-lived and susceptible to a reverse reaction that causes the reconstruction of original reactants. Antioxidants 2019, 8, 55 re-arrangement of atoms causing the development of Amadori products [1,2]. These are more durable than Schiff’s base and more prone toward the forward reaction. They undergo cyclization and dehydration to produce advanced glycation end products (AGEs), AGEs can be produced during the oxidation of lipids or nucleotides. AGEs are responsible for the onset and the evolution of several diseases, including obesity, nephropathy, diabetes, retinopathy, neuropathy, aging, and cardiovascular diseases [3]
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