Acetaldehyde-induced structural and conformational alterations in human immunoglobulin G: A physicochemical and multi-spectroscopic study

Waris, Sana; Habib, Safia; Tantry, Irfan Qadir; Khan, Rizwan Hasan; Mahmood, Riaz; Ali, Asif

doi:10.1016/j.ijbiomac.2018.03.013

Cited by 6 publications

(9 citation statements)

References 47 publications

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“…Gross structural changes were confirmed by increase in mass and hydrodynamic radii of IgG along with changes in morphology of the molecule as evident under scanning electron microscopy. These structural changes resulted in protein misfolding and loss in effector function of the molecule …”

Section: Resultsmentioning

confidence: 99%

“…These structural changes resulted in protein misfolding and loss in effector function of the molecule. 8…”

Section: Resultsmentioning

confidence: 99%

“…In our previous report, we performed a pilot study and established that 5 mM AA is the optimal concentration for modifying N‐IgG. We showed that AA binds strongly with IgG molecule via lysine residues and forms a strong covalent bond, followed by Lys‐Lys cross‐linking leading to the formation of a fluorescent adduct (2,6‐diamino hexanoic acid{1‐(N′‐[5‐amino‐1‐formyl‐pentyl]‐hydrazino)‐ethyl}‐amide) . In this study, we have performed the steady state fluorescence of tyrosine residue by exciting the samples at 275 nm and recording the emission in the range of 280 to 400 nm.…”

Section: Discussionmentioning

confidence: 97%

“…Acetaldehyde also reacts with other macromolecules such as DNA and low density lipoproteins . We have previously reported the formation of AA protein adduct with lysine residue of human IgG . Acetaldehyde is also known to react with other amino acids such as cysteine and alpha amino group of N‐terminal amino acids.…”

Section: Introductionmentioning

confidence: 99%

“…7 We have previously reported the formation of AA protein adduct with lysine residue of human IgG. 8 Acetaldehyde is also known to react with other amino acids such as cysteine and alpha amino group of N-terminal amino acids. Previous studies have reported that AA increases the secretion of TGF-β1 and induces TGF-β type II receptor expression in human hepatic stellate cells (HSCs).…”

Section: Introductionmentioning

confidence: 99%

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Molecular docking explores heightened immunogenicity and structural dynamics of acetaldehyde human immunoglobulin G adduct

et al. 2019

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Acetaldehyde is a metabolite of ethanol, an important constituent of tobacco pyrolysis and the aldehydic product of lipid peroxidation. Acetaldehyde induced toxicity is mainly due to its binding to cellular macromolecules resulting in the formation of stable adducts accompanied by oxidative stress. The aim of this study was to characterize structural and immunological alterations in human immunoglobulin G (IgG) modified with acetaldehyde in the presence of sodium borohydride, a reducing agent. The IgG modifications were studied by various physicochemical techniques such as fluorescence and CD spectroscopy, free amino group estimation, 2,2‐azobis 2‐amidinopropane (AAPH) induced red blood cell hemolysis as well as transmission electron microscopy. Molecular docking was also employed to predict the preferential binding of acetaldehyde to IgG. The immunogenicity of native and acetaldehyde‐modified IgG was investigated by immunizing female New Zealand white rabbits using native and modified IgG as antigens. Binding specificity and cross reactivity of rabbit antibodies was screened by competitive inhibition ELISA and band shift assays. The modification of human IgG with acetaldehyde results in quenching of the fluorescence of tyrosine residues, decrease in free amino group content, a change in the antioxidant property as well as formation of cross‐linked structures in human IgG. Molecular docking reveals strong binding of IgG to acetaldehyde. Moreover, acetaldehyde modified IgG induced high titer antibodies (>1:12800) in the experimental animals. The antibodies exhibited high specificity in competitive binding assay toward acetaldehyde modified human IgG. The results indicate that acetaldehyde induces alterations in secondary and tertiary structure of IgG molecule that leads to formation of neo‐epitopes on IgG that enhances its immunogenicity.

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Section: Resultsmentioning

confidence: 99%

“…These structural changes resulted in protein misfolding and loss in effector function of the molecule. 8…”

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 97%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Molecular docking explores heightened immunogenicity and structural dynamics of acetaldehyde human immunoglobulin G adduct

et al. 2019

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Synthesis of cationic carbon dots and their effects on human serum proteins and in vitro blood coagulation

et al. 2021

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Cationic carbon dots (CCDs) are a promising alternative to gene-delivery systems, and good biosafety levels are crucial for their in vivo use. In this study, spherical and monodispersed CCDs with an average surface potential of +28.7 mV were prepared using sucrose and glutamate (denoted SG-CCDs) using a one-pot autoclave-assisted method. Molecular interactions between the SG-CCDs and four major human serum proteins (albumin, immunoglobulin G, fibrinogen, and transferrin) were investigated.The results were further verified on human serum, and the effect of the SG-CCDs on in vitro blood coagulation was examined. The results showed that the fluorescence of human serum was clearly quenched by the SG-CCDs through a dynamic collision mechanism. Moreover, SG-CCDs at a concentration of 20 μM exhibited minor effects on the secondary structure of human serum. The activated partial thromboplastin and prothrombin time as well as the fibrinogen concentration were not changed, indicating that the SG-CCDs did not interfere with the coagulation process. This study provided an understandable background on the behaviour of CCDs in clinical applications.

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Acetaldehyde-induced oxidative modifications and morphological changes in isolated human erythrocytes: an in vitro study

Waris

Patel

Ali

et al. 2020

Environ Sci Pollut Res

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Acetaldehyde-induced structural and conformational alterations in human immunoglobulin G: A physicochemical and multi-spectroscopic study

Cited by 6 publications

References 47 publications

Molecular docking explores heightened immunogenicity and structural dynamics of acetaldehyde human immunoglobulin G adduct

Molecular docking explores heightened immunogenicity and structural dynamics of acetaldehyde human immunoglobulin G adduct

Synthesis of cationic carbon dots and their effects on human serum proteins and in vitro blood coagulation

Acetaldehyde-induced oxidative modifications and morphological changes in isolated human erythrocytes: an in vitro study

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