Hyperglycemia induced reactive species trigger structural changes in human serum albumin of type 1 diabetic subjects

• Published in: International journal of biological macromolecules Vol. 107; no. Pt B; pp. 2141 - 2149
• Main Authors: Arif, Zarina, Neelofar, Km, Arfat, Mir Yasir, Zaman, Asif, Tarannum, Akhlas, Parveen, Iffat, Ahmad, Shafeeque, Khan, Md Adnan, Badar, Asim, Islam, Shireen Naaz
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.02.2018
• Subjects: advanced glycation end products; antioxidant activity; Antioxidants - metabolism; autoimmunity; Biophysical Phenomena; Case-Control Studies; chlorine; Diabetes Mellitus, Type 1 - metabolism; epitopes; erythrocytes; Erythrocytes - metabolism; Erythrocytes - ultrastructure; fuels; Glycation; Hemolysis; Human serum albumin; Humans; Hydrophobic and Hydrophilic Interactions; Hyperglycemia; Hyperglycemia - metabolism; insulin; Iron - metabolism; islets of Langerhans; lipids; Mass Spectrometry; nitric oxide; Nitric Oxide - metabolism; nitrogen; oxidation; Oxidation-Reduction; oxidative stress; oxygen; pathogenesis; patients; post-translational modification; Protein Carbonylation; Reactive Oxygen Species - metabolism; Serum Albumin, Human - chemistry; Serum Albumin, Human - isolation & purification; Serum Albumin, Human - metabolism; Spectrum Analysis; sugars; Sulfhydryl Compounds - blood; thiols; Type1 diabetes mellitus; Type1 diabetes mellitus; Human serum albumin; Hyperglycemia; Glycation
• ISSN: 0141-8130; 1879-0003; 1879-0003
• DOI: 10.1016/j.ijbiomac.2017.10.091

Chronic oxidative stress fuels pathogenesis of a large set of diseases. Oxidative stress is the cause and consequence of numerous diseases including type 1 diabetes mellitus (T1DM), in which there is selective destruction of insulin producing pancreatic β-cells. Studies have documented that hyperglycemia produces profound stress. In vivo production of numerous reactive oxygen, nitrogen, chlorine species and lipid/sugar oxidation products in T1DM patients may be the result of persistent hyperglycemia. Post-translational modifications by reactive species may create new antigenic epitopes and play a role in the development of autoimmune response. In this paper our main focus was to establish the effect of existing hyperglycemia induced oxido-nitrosative stress in T1DM patients on the integrity of human serum albumin. Raised nitric oxide, carbonyl, RBC hemolysis, lowered ferric reducing antioxidant power (FRAP), thiol and deformed RBC in T1DM are all highly suggestive of persistent oxido-nitrosative stress. Hyperglycemia induced generation of advanced glycation end products (AGEs) was established by LCMS. Chronic oxido-nitrosative stress can modify HSA in T1DM patients, producing immunologically active albumin. Therefore, it is speculated that the aberrant HSA may play a role in the initiation/progression of T1DM.