title: Oxidative Stress Mediated Cytotoxicity of Glycated Albumin: Comparative Analysis of Glycation by Glucose Metabolites.
abstract: The non-enzymatic reaction between reducing sugars and proteins has received increased attention in nutritional and medical research recently. In the current manuscript, effect of glycation in structural changes of human serum albumin (HSA) by the metabolites of glucose such as glyoxal, methylglyoxal and glyceraldehyde was studied using different spectroscopy techniques. Glycation of HSA was monitored by following advanced glycation end-products (AGEs) fluorescence changes, HSA intrinsic fluorescence measurement, extrinsic fluorescence using 8-analino 1-nephthlene sulfonic acid (ANS) dye, and circular dichroism (CD) studies. AGEs were formed within 7 days of incubation with glyoxal, methylglyoxal and glyceraldehyde. However, methylglyoxal induced significant structural changes in HSA compared with glyoxal and glyceraldehydes. Moreover, ANS binding to native and glycated-HSA showed difference in binding pattern of these metabolites to HSA. The CD spectrum revealed changes in the secondary structure of HSA upon glycation when compared to native HSA. Furthermore, the MTT (3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl tetrazolium bromide) assay established the cytotoxicity of the glycated- HSA towards human liver carcinoma (HepG2) cell lines via the production of reactive oxygen species.
authors.affiliation: Protein Research Chair, Department of Biochemistry, College of Science, King Saud University, Riyadh, Saudi Arabia. moskhan@ksu.edu.sa.
authors.forename: Mohd Shahnawaz
authors.initials: MS
authors.lastname: Khan
authors.affiliation: King Fahd Medical Research Center, King Abdulaziz University, Jeddah, 21589, Saudi Arabia.
authors.forename: Shams
authors.initials: S
authors.lastname: Tabrez
authors.affiliation: Protein Research Chair, Department of Biochemistry, College of Science, King Saud University, Riyadh, Saudi Arabia.
authors.forename: Nayyar
authors.initials: N
authors.lastname: Rabbani
authors.affiliation: Department of Clinical Biochemistry, Sheri-Kashmir Institute of Medical Sciences, Soura, India.
authors.forename: Aaliya
authors.initials: A
authors.lastname: Shah
mesh_terms: D003603:Cytotoxins / Q000378:metabolism* / Q000633:toxicity*; D005947:Glucose / Q000378:metabolism*; D017127:Glycation End Products, Advanced; D006031:Glycosylation; D056945:Hep G2 Cells; D006801:Humans; D018384:Oxidative Stress / Q000187:drug effects*; D017382:Reactive Oxygen Species / Q000378:metabolism; D012709:Serum Albumin / Q000378:metabolism* / Q000633:toxicity*; D000093423:Glycated Serum Albumin
chemical_list: D003603:Cytotoxins; D017127:Glycation End Products, Advanced; D017382:Reactive Oxygen Species; D012709:Serum Albumin; D005947:Glucose; D000093423:Glycated Serum Albumin
keywords: Aggregation; Cytotoxicity; Glucose metabolites; Glycation