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.

Potential Antiglycation and Hypoglycaemic Effects ofToona ciliataM. Roem. andSchkuhria pinnataLam. Thell. Crude Extracts in Differentiated C2C12 Cells

“…On the other hand, only the methanol extract of S. pinnata showed promise as an antiglycation agent. Antiglycation agents can help in maintaining the proper function and structure of molecules that would have otherwise been rendered nonfunctional through the spontaneous Millard reaction [56]. To the best of our knowledge, this study reports the antiglycation potential of both S. pinnata and T. ciliata for the first time.…”

Vitamin D prevents glycation of proteins: an in vitro study

“…Modification of HSA can affect its affinity for various small molecules and drugs. This, in turn, may have varying consequences on metabolism and therapy of diabetes patients [5,29,30].…”

“…Its major binding regions are present in domain II and III, in an area called the Sudlows site. The Sudlows site 1 binds drugs like warfarin and phenylbutazone analogs; site 2 interacts with ibuprofen, diazepam and steroid derivatives [28,29]. Modification of HSA can affect its affinity for various small molecules and drugs.…”

Glycated albumin: a potential biomarker in diabetes

“…2017;61/3 is a normal process, conditions of typical hyperglycemia in patients with DM increase their production rates (26). AGEs receptors are present in cells of different tissues, such as macrophages, muscle, endothelial and glial cells (27).…”

“…They are expressed as membrane molecules, constituents of immunoglobulin superfamily and act as signal transduction receptors, inducing oxidative stress and starting an inflammatory cascade by activation of the nuclear factor-κB (NF-κB). NF-κB modulates the gene transcription of pro-inflammatory molecules such as interleukins 1, 6 and 8 and tumor necrosis factor-α, and also the vascular cell adhesion molecule-1 and intercellular adhesion molecule-1 (26). As a consequence of this cascade, there is an increased production of reactive oxygen species, which is directly associated with the pathogenesis and longterm complications in DM (21,27).…”