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Effect of Ergothioneine on 7-Ketocholesterol-Induced Endothelial Injury

Ergothioneine (ET) is a naturally occurring antioxidant that is synthesized by non-yeast fungi and certain bacteria. ET is not synthesized by animals, including humans, but is avidly taken up from the diet, especially from mushrooms. In the current study, we elucidated the effect of ET on the hCMEC/...

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Autores principales: Koh, Sally Shuxian, Ooi, Samantha Chia-Yi, Lui, Natalie Man-Yin, Qiong, Cao, Ho, Leona Ting-Yuke, Cheah, Irwin Kee-Mun, Halliwell, Barry, Herr, Deron R., Ong, Wei-Yi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer US 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7567423/
https://www.ncbi.nlm.nih.gov/pubmed/33067719
http://dx.doi.org/10.1007/s12017-020-08620-4
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author Koh, Sally Shuxian
Ooi, Samantha Chia-Yi
Lui, Natalie Man-Yin
Qiong, Cao
Ho, Leona Ting-Yuke
Cheah, Irwin Kee-Mun
Halliwell, Barry
Herr, Deron R.
Ong, Wei-Yi
author_facet Koh, Sally Shuxian
Ooi, Samantha Chia-Yi
Lui, Natalie Man-Yin
Qiong, Cao
Ho, Leona Ting-Yuke
Cheah, Irwin Kee-Mun
Halliwell, Barry
Herr, Deron R.
Ong, Wei-Yi
author_sort Koh, Sally Shuxian
collection PubMed
description Ergothioneine (ET) is a naturally occurring antioxidant that is synthesized by non-yeast fungi and certain bacteria. ET is not synthesized by animals, including humans, but is avidly taken up from the diet, especially from mushrooms. In the current study, we elucidated the effect of ET on the hCMEC/D3 human brain endothelial cell line. Endothelial cells are exposed to high levels of the cholesterol oxidation product, 7-ketocholesterol (7KC), in patients with cardiovascular disease and diabetes, and this process is thought to mediate pathological inflammation. 7KC induces a dose-dependent loss of cell viability and an increase in apoptosis and necrosis in the endothelial cells. A relocalization of the tight junction proteins, zonula occludens-1 (ZO-1) and claudin-5, towards the nucleus of the cells was also observed. These effects were significantly attenuated by ET. In addition, 7KC induces marked increases in the mRNA expression of pro-inflammatory cytokines, IL-1β IL-6, IL-8, TNF-α and cyclooxygenase-2 (COX2), as well as COX2 enzymatic activity, and these were significantly reduced by ET. Moreover, the cytoprotective and anti-inflammatory effects of ET were significantly reduced by co-incubation with an inhibitor of the ET transporter, OCTN1 (VHCL). This shows that ET needs to enter the endothelial cells to have a protective effect and is unlikely to act via extracellular neutralizing of 7KC. The protective effect on inflammation in brain endothelial cells suggests that ET might be useful as a nutraceutical for the prevention or management of neurovascular diseases, such as stroke and vascular dementia. Moreover, the ability of ET to cross the blood-brain barrier could point to its usefulness in combatting 7KC that is produced in the CNS during neuroinflammation, e.g. after excitotoxicity, in chronic neurodegenerative diseases, and possibly COVID-19-related neurologic complications.
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spelling pubmed-75674232020-10-19 Effect of Ergothioneine on 7-Ketocholesterol-Induced Endothelial Injury Koh, Sally Shuxian Ooi, Samantha Chia-Yi Lui, Natalie Man-Yin Qiong, Cao Ho, Leona Ting-Yuke Cheah, Irwin Kee-Mun Halliwell, Barry Herr, Deron R. Ong, Wei-Yi Neuromolecular Med Original Paper Ergothioneine (ET) is a naturally occurring antioxidant that is synthesized by non-yeast fungi and certain bacteria. ET is not synthesized by animals, including humans, but is avidly taken up from the diet, especially from mushrooms. In the current study, we elucidated the effect of ET on the hCMEC/D3 human brain endothelial cell line. Endothelial cells are exposed to high levels of the cholesterol oxidation product, 7-ketocholesterol (7KC), in patients with cardiovascular disease and diabetes, and this process is thought to mediate pathological inflammation. 7KC induces a dose-dependent loss of cell viability and an increase in apoptosis and necrosis in the endothelial cells. A relocalization of the tight junction proteins, zonula occludens-1 (ZO-1) and claudin-5, towards the nucleus of the cells was also observed. These effects were significantly attenuated by ET. In addition, 7KC induces marked increases in the mRNA expression of pro-inflammatory cytokines, IL-1β IL-6, IL-8, TNF-α and cyclooxygenase-2 (COX2), as well as COX2 enzymatic activity, and these were significantly reduced by ET. Moreover, the cytoprotective and anti-inflammatory effects of ET were significantly reduced by co-incubation with an inhibitor of the ET transporter, OCTN1 (VHCL). This shows that ET needs to enter the endothelial cells to have a protective effect and is unlikely to act via extracellular neutralizing of 7KC. The protective effect on inflammation in brain endothelial cells suggests that ET might be useful as a nutraceutical for the prevention or management of neurovascular diseases, such as stroke and vascular dementia. Moreover, the ability of ET to cross the blood-brain barrier could point to its usefulness in combatting 7KC that is produced in the CNS during neuroinflammation, e.g. after excitotoxicity, in chronic neurodegenerative diseases, and possibly COVID-19-related neurologic complications. Springer US 2020-10-16 2021 /pmc/articles/PMC7567423/ /pubmed/33067719 http://dx.doi.org/10.1007/s12017-020-08620-4 Text en © Springer Science+Business Media, LLC, part of Springer Nature 2020 This article is made available via the PMC Open Access Subset for unrestricted research re-use and secondary analysis in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic.
spellingShingle Original Paper
Koh, Sally Shuxian
Ooi, Samantha Chia-Yi
Lui, Natalie Man-Yin
Qiong, Cao
Ho, Leona Ting-Yuke
Cheah, Irwin Kee-Mun
Halliwell, Barry
Herr, Deron R.
Ong, Wei-Yi
Effect of Ergothioneine on 7-Ketocholesterol-Induced Endothelial Injury
title Effect of Ergothioneine on 7-Ketocholesterol-Induced Endothelial Injury
title_full Effect of Ergothioneine on 7-Ketocholesterol-Induced Endothelial Injury
title_fullStr Effect of Ergothioneine on 7-Ketocholesterol-Induced Endothelial Injury
title_full_unstemmed Effect of Ergothioneine on 7-Ketocholesterol-Induced Endothelial Injury
title_short Effect of Ergothioneine on 7-Ketocholesterol-Induced Endothelial Injury
title_sort effect of ergothioneine on 7-ketocholesterol-induced endothelial injury
topic Original Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7567423/
https://www.ncbi.nlm.nih.gov/pubmed/33067719
http://dx.doi.org/10.1007/s12017-020-08620-4
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