Background: Non-enzymatic glycation of proteins plays a significant role in the pathogenesis of secondary diabetic complications via the formation of advanced glycation end products (AGEs) and increased oxidative stress. Methylglyoxal (MG), a highly reactive dicarbonyl of class α-oxoaldehyde that generates during glucose oxidation and lipid peroxidation, contributes to glycation.
Objective: This comparative study focuses on methylglyoxal induced glycoxidative damage suffered by immunoglobulin G (IgG) and fibrinogen, and to unveil implication of structural modification of serum proteins in diabetes-associated secondary complications.
Methods: The methylglyoxal induced structural alterations in IgG and fibrinogen were analyzed by UVvis, fluorescence, circular dichroism and Fourier transform infrared (FT-IR) spectroscopy. Ketoamine moieties, carbonyl contents, 5-Hydroxymethylfurfural (HMF) and malondyaldehyde were also quantified. Free lysine and arginine estimation, detection of non-fluorogenic carboxymethyllysine (CML) and fibril formation were confirmed by thioflavin T (ThT) assay.
Results: Structural alterations, increased carbonyl contents and ketoamines were reported in MG glycated IgG and fibrinogen against their native analogues.
Conclusion: The experiment results validate structural modifications, increased oxidative stress and AGEs formation. Thus, we can conclude that IgG-AGEs and Fib-AGEs formed during MG induced glycation of IgG and fibrinogen could impede normal physiology and might initiates secondary complications in diabetic patients.
[http://dx.doi.org/10.3390/ijms18050984] [PMID: 28475116]
[http://dx.doi.org/10.1093/glycob/cwv082 ] [PMID: 26408820 ]
[http://dx.doi.org/10.1002/art.27533] [PMID: 20506563]
[http://dx.doi.org/10.1371/journal.pone.0116804 ] [PMID: 25689368 ]
[http://dx.doi.org/10.1042/bj2910529] [PMID: 8484733]