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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...

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Autores principales: 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.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5589919/
https://www.ncbi.nlm.nih.gov/pubmed/28883613
http://dx.doi.org/10.1038/s41598-017-11289-8
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author 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.
author_facet 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.
author_sort Nakamura, Jun
collection PubMed
description 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.
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spelling pubmed-55899192017-09-13 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 S. Gold, Avram Bultman, Scott J. Sci Rep Article 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. Nature Publishing Group UK 2017-09-07 /pmc/articles/PMC5589919/ /pubmed/28883613 http://dx.doi.org/10.1038/s41598-017-11289-8 Text en © The Author(s) 2017 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
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.
Evidence that endogenous formaldehyde produces immunogenic and atherogenic adduct epitopes
title Evidence that endogenous formaldehyde produces immunogenic and atherogenic adduct epitopes
title_full Evidence that endogenous formaldehyde produces immunogenic and atherogenic adduct epitopes
title_fullStr Evidence that endogenous formaldehyde produces immunogenic and atherogenic adduct epitopes
title_full_unstemmed Evidence that endogenous formaldehyde produces immunogenic and atherogenic adduct epitopes
title_short Evidence that endogenous formaldehyde produces immunogenic and atherogenic adduct epitopes
title_sort evidence that endogenous formaldehyde produces immunogenic and atherogenic adduct epitopes
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5589919/
https://www.ncbi.nlm.nih.gov/pubmed/28883613
http://dx.doi.org/10.1038/s41598-017-11289-8
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