Impact of in vitro non-enzymatic glycation on biophysical and biochemical regimes of human serum albumin: relevance in diabetes associated complications

Neelofar,; Ahmad, Jamal; Alam, Khursheed

doi:10.1039/c5ra07232h

Cited by 41 publications

(15 citation statements)

References 38 publications

(64 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The78.3% hyperchromicity in UV absorbance values forOH • -MG modifiedIgGas compared to 55.9% and 64.7% for OH • -IgG and MG-IgG samples, when compared with N-IgG, suggests a stronger structural damage of IgG by OH • -MG. IgG modified by OH • -MG reflect highly exposed chromophoric aromatic amino acid residues, indicating extensive structural perturbations in the molecule.Appearance of a hump like structure in MG-IgG and OH • -MG-IgG indicate the formation of AGEs. Similar changes in absorbance have been reported earlier[45, 46]. Fluorescence spectroscopy is a valuable parameter to monitor microenvironment around aromatic amino acid residues [47].…”

Section: Discussionsupporting

confidence: 79%

Neo-Epitopes Generated on Hydroxyl Radical Modified GlycatedIgG Have Role in Immunopathology of Diabetes Type 2

et al. 2017

Self Cite

View full text Add to dashboard Cite

Glycoxidation plays a crucial role in diabetes and its associated complications. Among the glycoxidation agents, methylglyoxal (MG) is known to have very highglycationpotential witha concomitant generation of reactive oxygen species (ROS) during its synthesis and degradation. The presentstudy probes the MG and ROSinduced structural damage to immunoglobulin G (IgG) and alterations in its immunogenicity in diabetes type 2 patients (T2DM). Human IgG was first glycated with MG followed by hydroxyl radical (OH•) modification. Glycoxidation mediated effects on IgG were evaluated by various physicochemical techniques likeultraviolet (UV) and fluorescence spectroscopy, 8-anilinonaphthalene-1-sulfonic acid (ANS) binding studies, carbonyl andfree sulfhydryl groups assay, matrix assisted laser desorption ionization mass spectrometry-time of flight (MALDI-TOF), red blood cell (RBC) haemolysis assay, Congored (CR) staining analysis and scanning electron microscopy (SEM). The results revealed hyperchromicityin UV, advanced glycation end product (AGE)specific and ANS fluorescence, quenching in tyrosine and tryptophan fluorescence intensity,enhanced carbonyl content,reduction in free sulfhydryl groups,pronounced shift in m/z value of IgGand decrease in antioxidant activity in RBC induced haemolysis assayupon glycoxidation. SEM and CRstaining assay showed highly altered surface morphology in glycoxidised sample as compared to the native. Enzyme linked immunosorbent assay (ELISA) and band shift assay were performed to assess the changes in immunogenicity of IgG upon glyoxidation and its role in T2DM. The serum antibodies derived from T2DM patients demonstrated strong affinity towards OH• treated MG glycatedIgG (OH•-MG-IgG) when compared to native IgG (N-IgG) or IgGs treated with MG alone (MG-IgG) or OH• alone (OH•-IgG). This study shows the cumulating effect of OH• on the glycation potential of MG. The results point towards the modification of IgG in diabetes patients under the effect of glycoxidative stress, leading to the generation of neo-epitopes on theIgG molecule and rendering it immunogenic.

show abstract

Section: Discussionsupporting

confidence: 79%

Neo-Epitopes Generated on Hydroxyl Radical Modified GlycatedIgG Have Role in Immunopathology of Diabetes Type 2

et al. 2017

Self Cite

View full text Add to dashboard Cite

show abstract

“…We also found the newly generated chromophores in the event of glycation; a new characteristic peak of significant absorbance could be seen between 300 and 400 nm . It suggested that MGO induced a structural alteration of BSA and AGEs was generated …”

Section: Resultsmentioning

confidence: 65%

Eriodictyol and naringenin inhibit the formation of AGEs: An in vitro and molecular interaction study

Liu

Yang

Cheng

et al. 2019

J of Molecular Recognition

View full text Add to dashboard Cite

Maillard reaction occurs between the carbonyl group of reducing sugars and the free amino groups of protein, which eventually results in the formation and accumulation of advanced glycation end products (AGEs) irreversibly. Excessive production of AGEs is associated with many diseases, such as Alzheimer disease, neuropathy, retinopathy, and nephropathy. In this study, the effects of eriodictyol and naringenin

show abstract

“…Tissue AGE deposition is largely responsible for complications arising in diabetes [36]. It also limits the antioxidant properties of HSA which depends on the presence of free thiol groups [37].…”

Section: Discussionmentioning

confidence: 99%

Vitamin D prevents glycation of proteins: an in vitro study

2016

View full text Add to dashboard Cite

Human serum albumin (HSA) is an important protein involved in the transport of hormones, fatty acids, drugs, and other macromolecules. Under hyperglycemic conditions, this molecule undergoes irreversible modification that affects its structure and function. In this study, we explored the effect of two forms of vitamin D, a nutraceutical, on glycation modification in HSA. The protein was incubated with a physiologically high concentration of glucose in the presence of vitamin D metabolites. After 21 days, samples were tested for secondary structural changes, side chain modification, and the presence of advanced glycation end products. Vitamin D metabolites could reduce glycation modification, albeit only to a small extent. Interaction studies reveal that Vitamin D interaction with HSA can prevent protein glycation.Keywords: calcitriol; glycation; protein Type 2 Diabetes is a global health issue growing at an unprecedented rate. The disease accounts for 90% of diabetes cases worldwide and is characterized by defects in glucose metabolism [1]. Persistently high blood glucose concentration encountered in diabetes often initiates Maillard reaction which causes nonenzymatic glycation of proteins and yields a plethora of reactive compounds called advanced glycation end products (AGEs) [2].Modification of protein structure and function by AGEs is consistent with the progression of diabetic complications and correlates positively with the severity of conditions like retinopathy, neuropathy, and nephropathy [3]. Once initiated, AGEs formation continues throughout the lifespan of proteins, and cannot be reversed by normalizing hyperglycemia [2,4].Human serum albumin (HSA) frequently undergoes Maillard reaction to from covalently cross-linked composites [3]. In normal adults, 6-10% of lysine chains are modified by nonenzymatic glycation, however, this number increases by 2-3 folds in individuals suffering from diabetes [5]. This may interfere with HSA function [5]. Since HSA is involved in the transportation of several moieties: nutrients, steroids, and a wide variety of drugs this can have detrimental physiological effects [6].Research suggests that vitamin D is involved in controlling AGE-associated damage in both diabetes and heart disorders [7]. Vitamin D is a fat-soluble micronutrient which is produced in the body by UV irradiation of a precursor steroid stored in the skin. The functionally active form of vitamin D, calcitriol, has a wide array of health implications [8]. Multiple studies have demonstrated its ability in limiting oxidative damage and regulating the status of a potent cellular antioxidant-reduced glutathione (GSH) [7]. Vitamin D deficiency is thought to be a risk factor for the development of diabetes; Low vitamin D status is associated with increased insulin resistance, glycated hemoglobin (HbA1c), and AGE formation [9][10][11]. Previous reports have correlated low circulating concentrations of vitamin D with increased risk of diabetic macrovascular and microvascular complications: mainly nephropathy a...

show abstract

Impact of in vitro non-enzymatic glycation on biophysical and biochemical regimes of human serum albumin: relevance in diabetes associated complications

Cited by 41 publications

References 38 publications

Neo-Epitopes Generated on Hydroxyl Radical Modified GlycatedIgG Have Role in Immunopathology of Diabetes Type 2

Neo-Epitopes Generated on Hydroxyl Radical Modified GlycatedIgG Have Role in Immunopathology of Diabetes Type 2

Eriodictyol and naringenin inhibit the formation of AGEs: An in vitro and molecular interaction study

Vitamin D prevents glycation of proteins: an in vitro study

Contact Info

Product

Resources

About