New insights into deleterious impacts of in vivo glycation on albumin antioxidant activities

• Published in: Biochimica et biophysica acta Vol. 1830; no. 6; pp. 3532 - 3541
• Main Authors: Baraka-Vidot, Jennifer, Guerin-Dubourg, Alexis, Dubois, Fanny, Payet, Bertrand, Bourdon, Emmanuel, Rondeau, Philippe
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.06.2013; Elsevier
• Subjects: adipocytes; Advanced glycation end-products; Albumin; albumins; anti-inflammatory activity; Antioxidant; antioxidant activity; antioxidants; Antioxidants - metabolism; Cell Line, Tumor; Chemical Sciences; cultured cells; Diabetes; Diabetes Mellitus - metabolism; Female; Gene Expression Regulation; gene induction; Glycation; hemolysis; Humans; Inflammation; interleukin-6; macrophages; Male; metabolism; Models, Biological; NF-kappa B - metabolism; Oxidative Stress; patients; Protein Processing, Post-Translational; reactive oxygen species; Receptor for Advanced Glycation End Products; Receptors, Immunologic - biosynthesis; secretion; Serum Albumin - metabolism; transcription factor NF-kappa B; PBS; Advanced glycation end-products; HSA-ND and HSA-D; HSA; Albumin; Inflammation; Diabetes; Antioxidant; HbA1C; Glycation; AGE
• ISSN: 0304-4165; 0006-3002; 1872-8006
• DOI: 10.1016/j.bbagen.2013.01.019

Albumin constitutes the most abundant circulating antioxidant and prevents oxidative damages. However, in diabetes, this plasmatic protein is exposed to several oxidative modifications, which impact on albumin antioxidant properties. Most studies dealing on albumin antioxidant activities were conducted on in vitro modified protein. Here we tried to decipher whether reduced antioxidant properties of albumin could be evidenced in vivo. For this, we compared the antioxidant properties of albumin purified from diabetic patients to in vitro models of glycated albumin. Both in vivo and in vitro glycated albumins displayed impaired antioxidant activities in the free radical-induced hemolysis test. Surprisingly, the ORAC method (Oxygen Radical Antioxidant Capacity) showed an enhanced antioxidant activity for glycated albumin. Faced with this paradox, we investigated antioxidant and anti-inflammatory activities of our albumin preparations on cultured cells (macrophages and adipocytes). Reduced cellular metabolism and enhanced intracellular oxidative stress were measured in cells treated with albumin from diabetics. NF-kB –mediated gene induction was higher in macrophages treated with both type of glycated albumin compared with cells treated with native albumin. Anti inflammatory activity of native albumin is significantly impaired after in vitro glycation and albumin purified from diabetics significantly enhanced IL6 secretion by adipocytes. Expression of receptor for advanced glycation products is significantly enhanced in glycated albumin-treated cells. Our results bring new evidences on the deleterious impairments of albumin important functions after glycation and emphasize the importance of in vivo model of glycation in studies relied to diabetes pathology. ► Enhanced glycative modification of albumin in diabetes. ► Effect of in vitro and in vivo glycated albumin on macrophages and adipocytes. ► Impaired anti-oxidant/inflammatory properties of albumin purified from diabetics.