Malondialdehyde-Induced Post-translational Modifications in Hemoglobin of Smokers by NanoLC-NSI/MS/MS Analysis

Malondialdehyde (MDA) is the most abundant α,β-unsaturated aldehyde generated from endogenous peroxidation of polyunsaturated fatty acids and is present in cigarette smoke. Post-translational modifications of blood hemoglobin can serve as biomarkers for exposure to chemicals. In this study, two type...

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Bibliographic Details
Published in:Journal of proteome research Vol. 21; no. 12; p. 2947
Main Authors: Chen, Hauh-Jyun Candy, Chen, Chau-Yi, Fang, Ya-Hsuan, Hung, Kai-Wei, Wu, Deng-Chyang
Format: Journal Article
Language:English
Published: United States 02.12.2022
Subjects:
Biomarkers - metabolism
Hemoglobins - chemistry
Humans
Lysine - metabolism
Malondialdehyde
Protein Processing, Post-Translational
Smokers
Tandem Mass Spectrometry
posttranslational modifications
malondialdehyde
biomarker
selected reaction monitoring
hemoglobin
smoking
ISSN:1535-3907, 1535-3907
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Summary:Malondialdehyde (MDA) is the most abundant α,β-unsaturated aldehyde generated from endogenous peroxidation of polyunsaturated fatty acids and is present in cigarette smoke. Post-translational modifications of blood hemoglobin can serve as biomarkers for exposure to chemicals. In this study, two types of MDA-induced modifications, the -propenal and the dihydropyridine (DHP), were identified at multiple sites in human hemoglobin digest by the high-resolution mass spectrometry. The -propenal and the DHP types of modification led to the increase of 54.0106 and 134.0368 amu, respectively, at the -terminal and lysine residues. Among the 21 MDA-modified peptides, 14 with dose-response to MDA concentrations were simultaneously quantified in study subjects by the nanoflow liquid chromatography nanoelectrospray ionization tandem mass spectrometry under selected reaction monitoring (nanoLC-NSI-MS/MS-SRM) without prior enrichment. The results showed that the modifications of the -propenal-type at α-Lys-11, α-Lys-16, α-Lys-61, β-Lys-8, and β-Lys-17, as well as the DHP-type at the α- -terminal valine, are significantly higher in hemoglobin isolated from the blood of smokers than in nonsmoking individuals. This is the first report to identify and quantify multiple sites of MDA-induced modifications in human hemoglobin from peripheral blood. Our results suggest that the MDA-derived modifications on hemoglobin might represent valuable biomarkers for MDA-induced protein damage.
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ISSN:1535-3907
1535-3907
DOI:10.1021/acs.jproteome.2c00442