Evidence that endogenous formaldehyde produces immunogenic and atherogenic adduct epitopes

Endogenous formaldehyde is abundantly present in our bodies, at around 100 µM under normal conditions. While such high steady state levels of formaldehyde may be derived by enzymatic reactions including oxidative demethylation/deamination and myeloperoxidation, it is unclear whether endogenous forma...

Full description

Saved in:
Bibliographic Details
Published in:Scientific reports 2017-09, Vol.7 (1), p.10787-12, Article 10787
Main Authors: Nakamura, Jun, Shimomoto, Takasumi, Collins, Leonard B., Holley, Darcy W., Zhang, Zhenfa, Barbee, Jenna M., Sharma, Vyom, Tian, Xu, Kondo, Tomohiro, Uchida, Koji, Yi, Xianwen, Perkins, Diana O., Willis, Monte S., Gold, Avram, Bultman, Scott J.
Format: Article
Language:English
Subjects:
13/1
13/51
140/131
631/1647/664/1467
631/92/2783
692/4019/592/75/593/2100
Adducts
Adjuvants
Aortic valve
Apolipoprotein E
Arteriosclerosis
Atherogenesis
Atherosclerosis
Deamination
Degenerative diseases
Demethylation
Dihydropyridine
Epitopes
Formaldehyde
Glycine
Humanities and Social Sciences
Hydrogen peroxide
Immunogenicity
Lysine
Malondialdehyde
multidisciplinary
Peroxidase
Science
Science (multidisciplinary)
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Endogenous formaldehyde is abundantly present in our bodies, at around 100 µM under normal conditions. While such high steady state levels of formaldehyde may be derived by enzymatic reactions including oxidative demethylation/deamination and myeloperoxidation, it is unclear whether endogenous formaldehyde can initiate and/or promote diseases in humans. Here, we show that fluorescent malondialdehyde-formaldehyde (M2FA)-lysine adducts are immunogenic without adjuvants in mice. Natural antibody titers against M2FA are elevated in atherosclerosis-prone mice. Staining with an antibody against M2FA demonstrated that M2FA is present in plaque found on the aortic valve of ApoE −/− mice. To mimic inflammation during atherogenesis, human myeloperoxidase was incubated with glycine, H 2 O 2 , malondialdehyde, and a lysine analog in PBS at a physiological temperature, which resulted in M2FA generation. These results strongly suggest that the 1,4-dihydropyridine-type of lysine adducts observed in atherosclerosis lesions are likely produced by endogenous formaldehyde and malondialdehyde with lysine. These highly fluorescent M2FA adducts may play important roles in human inflammatory and degenerative diseases.
ISSN:2045-2322
2045-2322
DOI:10.1038/s41598-017-11289-8