Deletion of the lactoperoxidase gene causes multisystem inflammation and tumors in mice

Abstract Strongly oxidative H2O2 is biologically important, but if uncontrolled, would lead to tissue injuries. Lactoperoxidase (LPO) catalyzes the redox reaction of reducing highly reactive H2O2 to H2O while oxidizing thiocyanate (SCN−) to relatively tissue-innocuous hypothiocyanite (OSCN−). SCN− i...

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Autores principales:	Jayden Yamakaze, Zhe Lu
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/1693411c90e147f0b61048156d38be4c
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spelling	oai:doaj.org-article:1693411c90e147f0b61048156d38be4c2021-12-02T17:24:10ZDeletion of the lactoperoxidase gene causes multisystem inflammation and tumors in mice10.1038/s41598-021-91745-82045-2322https://doaj.org/article/1693411c90e147f0b61048156d38be4c2021-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-91745-8https://doaj.org/toc/2045-2322Abstract Strongly oxidative H2O2 is biologically important, but if uncontrolled, would lead to tissue injuries. Lactoperoxidase (LPO) catalyzes the redox reaction of reducing highly reactive H2O2 to H2O while oxidizing thiocyanate (SCN−) to relatively tissue-innocuous hypothiocyanite (OSCN−). SCN− is the only known natural, effective reducing-substrate of LPO; humans normally derive SCN− solely from food. While its enzymatic mechanism is understood, the actual biological role of the LPO-SCN− system in mammals remains unestablished. Our group previously showed that this system protected cultured human cells from H2O2-caused injuries, a basis for the hypothesis that general deficiency of such an antioxidative mechanism would lead to multisystem inflammation and tumors. To test this hypothesis, we globally deleted the Lpo gene in mice. The mutant mice exhibited inflammation and lesions in the cardiovascular, respiratory, digestive or excretory systems, neuropathology, and tumors, with high incidence. Thus, this understudied LPO-SCN− system is an essential protective mechanism in vivo.Jayden YamakazeZhe LuNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-16 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Jayden Yamakaze Zhe Lu Deletion of the lactoperoxidase gene causes multisystem inflammation and tumors in mice
description	Abstract Strongly oxidative H2O2 is biologically important, but if uncontrolled, would lead to tissue injuries. Lactoperoxidase (LPO) catalyzes the redox reaction of reducing highly reactive H2O2 to H2O while oxidizing thiocyanate (SCN−) to relatively tissue-innocuous hypothiocyanite (OSCN−). SCN− is the only known natural, effective reducing-substrate of LPO; humans normally derive SCN− solely from food. While its enzymatic mechanism is understood, the actual biological role of the LPO-SCN− system in mammals remains unestablished. Our group previously showed that this system protected cultured human cells from H2O2-caused injuries, a basis for the hypothesis that general deficiency of such an antioxidative mechanism would lead to multisystem inflammation and tumors. To test this hypothesis, we globally deleted the Lpo gene in mice. The mutant mice exhibited inflammation and lesions in the cardiovascular, respiratory, digestive or excretory systems, neuropathology, and tumors, with high incidence. Thus, this understudied LPO-SCN− system is an essential protective mechanism in vivo.
format	article
author	Jayden Yamakaze Zhe Lu
author_facet	Jayden Yamakaze Zhe Lu
author_sort	Jayden Yamakaze
title	Deletion of the lactoperoxidase gene causes multisystem inflammation and tumors in mice
title_short	Deletion of the lactoperoxidase gene causes multisystem inflammation and tumors in mice
title_full	Deletion of the lactoperoxidase gene causes multisystem inflammation and tumors in mice
title_fullStr	Deletion of the lactoperoxidase gene causes multisystem inflammation and tumors in mice
title_full_unstemmed	Deletion of the lactoperoxidase gene causes multisystem inflammation and tumors in mice
title_sort	deletion of the lactoperoxidase gene causes multisystem inflammation and tumors in mice
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/1693411c90e147f0b61048156d38be4c
work_keys_str_mv	AT jaydenyamakaze deletionofthelactoperoxidasegenecausesmultisysteminflammationandtumorsinmice AT zhelu deletionofthelactoperoxidasegenecausesmultisysteminflammationandtumorsinmice
_version_	1718380892420833280

Deletion of the lactoperoxidase gene causes multisystem inflammation and tumors in mice

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