Evidence that endogenous formaldehyde produces immunogenic and atherogenic adduct epitopes

Jun Nakamura, Takasumi Shimomoto, Leonard B. Collins, Darcy W. Holley, Zhenfa Zhang, Jenna M. Barbee, Vyom Sharma, Xu Tian, Tomohiro Kondo, Koji Uchida, Xianwen Yi, DIana O. Perkins, Monte Willis, Avram Gold, Scott J. Bultman

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Article number10787
JournalScientific Reports
Volume7
Issue number1
DOIs
StatePublished - Dec 1 2017
Externally publishedYes

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Formaldehyde
Epitopes
Lysine
Malondialdehyde
Atherosclerosis
Deamination
Antibodies
Apolipoproteins E
Aortic Valve
Glycine
Peroxidase
Staining and Labeling
Inflammation
Temperature

ASJC Scopus subject areas

  • General

Cite this

Nakamura, J., Shimomoto, T., Collins, L. B., Holley, D. W., Zhang, Z., Barbee, J. M., ... Bultman, S. J. (2017). Evidence that endogenous formaldehyde produces immunogenic and atherogenic adduct epitopes. Scientific Reports, 7(1), [10787]. https://doi.org/10.1038/s41598-017-11289-8

Evidence that endogenous formaldehyde produces immunogenic and atherogenic adduct epitopes. / 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; Gold, Avram; Bultman, Scott J.

In: Scientific Reports, Vol. 7, No. 1, 10787, 01.12.2017.

Research output: Contribution to journalArticle

Nakamura, J, Shimomoto, T, Collins, LB, Holley, DW, Zhang, Z, Barbee, JM, Sharma, V, Tian, X, Kondo, T, Uchida, K, Yi, X, Perkins, DIO, Willis, M, Gold, A & Bultman, SJ 2017, 'Evidence that endogenous formaldehyde produces immunogenic and atherogenic adduct epitopes', Scientific Reports, vol. 7, no. 1, 10787. https://doi.org/10.1038/s41598-017-11289-8
Nakamura J, Shimomoto T, Collins LB, Holley DW, Zhang Z, Barbee JM et al. Evidence that endogenous formaldehyde produces immunogenic and atherogenic adduct epitopes. Scientific Reports. 2017 Dec 1;7(1). 10787. https://doi.org/10.1038/s41598-017-11289-8
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 ; Gold, Avram ; Bultman, Scott J. / Evidence that endogenous formaldehyde produces immunogenic and atherogenic adduct epitopes. In: Scientific Reports. 2017 ; Vol. 7, No. 1.
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