Glycation promotes the formation of genotoxic aggregates in glucose oxidase

Abstract

This study investigates the effect of pentose sugars (ribose and arabinose) on the structural and chemical modifications in glucose oxidase (GOD) as well as genotoxic potential of this modified form. An intermediate state of GOD was observed on day 12 of incubation having CD minima peaks at 222 and 208 nm, characteristic of α-helix and a few tertiary contacts with altered tryptophan environment and high ANS binding. All these features indicate the existence of molten globule state of the GOD with ribose and arabinose on day 12. GOD on day 15 of incubation forms β structures as revealed by CD and FTIR which may be due to its aggregation. Furthermore, GOD on day 15 showed a remarkable increase in Thioflavin T fluorescence at 485 nm. Comet assay of lymphocytes and plasmid nicking assay in presence of glycated GOD show DNA damage which confirmed the genotoxicity of advance glycated end products. Hence, our study suggests that glycated GOD results in the formation of aggregates and the advanced glycated end products, which are genotoxic in nature.

Deciphering Structural Intermediates and Genotoxic Fibrillar Aggregates of Albumins: A Molecular Mechanism Underlying for Degenerative Diseases

“…Incubation was performed at 37°C for 1 h. After incubation, the reaction mixture was centrifuged at 716.8 g, the supernatant was discarded and pelleted lymphocytes were resuspended in 100 µL of PBS and processed further for SCGE assay. SCGE assay of protein aggregates was performed under alkaline conditions by the procedure of Khan et al [28].…”

Molten Globule of Hemoglobin Proceeds into Aggregates and Advanced Glycated End Products

“…These results suggest that genotoxic effect is predominantly observed in glycated Hb relative to aggregated Hb in vitro. These aggregates and AGEs being small in size might get penetrated into the nuclear pore complex and caused the DNA damage [38].…”

A novel glucose biosensor based on phosphonic acid-functionalized silica nanoparticles for sensitive detection of glucose in real samples

“…2 showed the CD spectrum of GOD in the PBS after bioconjugate with PFSi NPs and silica NPs in the far-UV region, respectively. The positive bands at 202 nm and two negative bands at around 208 and 219 nm arised in curve (a), curve (b) and curve (c) are corresponded to the -* transition and n-* transition of the amide groups in the GOD peptide chain [28]. Band of GOD/(PFSi NPs) looked almost as same as pure GOD, only the intensity of the dual bands at 208 and 219 nm had a slight increase, indicating that the secondary structure of GOD was not obviously changed.…”