Methylselenol formed by spontaneous methylation of selenide is a superior selenium substrate to the thioredoxin and glutaredoxin systems.

Naturally occurring selenium compounds like selenite and selenodiglutathione are metabolized to selenide in plants and animals. This highly reactive form of selenium can undergo methylation and form monomethylated and multimethylated species. These redox active selenium metabolites are of particular...

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Autores principales:	Aristi P Fernandes, Marita Wallenberg, Valentina Gandin, Sougat Misra, Francesco Tisato, Cristina Marzano, Maria Pia Rigobello, Sushil Kumar, Mikael Björnstedt
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2012
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/40d6f706fb004e53af57426628f8b27f
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spelling	oai:doaj.org-article:40d6f706fb004e53af57426628f8b27f2021-11-18T08:06:44ZMethylselenol formed by spontaneous methylation of selenide is a superior selenium substrate to the thioredoxin and glutaredoxin systems.1932-620310.1371/journal.pone.0050727https://doaj.org/article/40d6f706fb004e53af57426628f8b27f2012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23226364/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203Naturally occurring selenium compounds like selenite and selenodiglutathione are metabolized to selenide in plants and animals. This highly reactive form of selenium can undergo methylation and form monomethylated and multimethylated species. These redox active selenium metabolites are of particular biological and pharmacological interest since they are potent inducers of apoptosis in cancer cells. The mammalian thioredoxin and glutaredoxin systems efficiently reduce selenite and selenodiglutathione to selenide. The reactions are non-stoichiometric aerobically due to redox cycling of selenide with oxygen and thiols. Using LDI-MS, we identified that the addition of S-adenosylmethionine (SAM) to the reactions formed methylselenol. This metabolite was a superior substrate to both the thioredoxin and glutaredoxin systems increasing the velocities of the nonstoichiometric redox cycles three-fold. In vitro cell experiments demonstrated that the presence of SAM increased the cytotoxicity of selenite and selenodiglutathione, which could neither be explained by altered selenium uptake nor impaired extra-cellular redox environment, previously shown to be highly important to selenite uptake and cytotoxicity. Our data suggest that selenide and SAM react spontaneously forming methylselenol, a highly nucleophilic and cytotoxic agent, with important physiological and pharmacological implications for the highly interesting anticancer effects of selenium.Aristi P FernandesMarita WallenbergValentina GandinSougat MisraFrancesco TisatoCristina MarzanoMaria Pia RigobelloSushil KumarMikael BjörnstedtPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 7, Iss 11, p e50727 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Aristi P Fernandes Marita Wallenberg Valentina Gandin Sougat Misra Francesco Tisato Cristina Marzano Maria Pia Rigobello Sushil Kumar Mikael Björnstedt Methylselenol formed by spontaneous methylation of selenide is a superior selenium substrate to the thioredoxin and glutaredoxin systems.
description	Naturally occurring selenium compounds like selenite and selenodiglutathione are metabolized to selenide in plants and animals. This highly reactive form of selenium can undergo methylation and form monomethylated and multimethylated species. These redox active selenium metabolites are of particular biological and pharmacological interest since they are potent inducers of apoptosis in cancer cells. The mammalian thioredoxin and glutaredoxin systems efficiently reduce selenite and selenodiglutathione to selenide. The reactions are non-stoichiometric aerobically due to redox cycling of selenide with oxygen and thiols. Using LDI-MS, we identified that the addition of S-adenosylmethionine (SAM) to the reactions formed methylselenol. This metabolite was a superior substrate to both the thioredoxin and glutaredoxin systems increasing the velocities of the nonstoichiometric redox cycles three-fold. In vitro cell experiments demonstrated that the presence of SAM increased the cytotoxicity of selenite and selenodiglutathione, which could neither be explained by altered selenium uptake nor impaired extra-cellular redox environment, previously shown to be highly important to selenite uptake and cytotoxicity. Our data suggest that selenide and SAM react spontaneously forming methylselenol, a highly nucleophilic and cytotoxic agent, with important physiological and pharmacological implications for the highly interesting anticancer effects of selenium.
format	article
author	Aristi P Fernandes Marita Wallenberg Valentina Gandin Sougat Misra Francesco Tisato Cristina Marzano Maria Pia Rigobello Sushil Kumar Mikael Björnstedt
author_facet	Aristi P Fernandes Marita Wallenberg Valentina Gandin Sougat Misra Francesco Tisato Cristina Marzano Maria Pia Rigobello Sushil Kumar Mikael Björnstedt
author_sort	Aristi P Fernandes
title	Methylselenol formed by spontaneous methylation of selenide is a superior selenium substrate to the thioredoxin and glutaredoxin systems.
title_short	Methylselenol formed by spontaneous methylation of selenide is a superior selenium substrate to the thioredoxin and glutaredoxin systems.
title_full	Methylselenol formed by spontaneous methylation of selenide is a superior selenium substrate to the thioredoxin and glutaredoxin systems.
title_fullStr	Methylselenol formed by spontaneous methylation of selenide is a superior selenium substrate to the thioredoxin and glutaredoxin systems.
title_full_unstemmed	Methylselenol formed by spontaneous methylation of selenide is a superior selenium substrate to the thioredoxin and glutaredoxin systems.
title_sort	methylselenol formed by spontaneous methylation of selenide is a superior selenium substrate to the thioredoxin and glutaredoxin systems.
publisher	Public Library of Science (PLoS)
publishDate	2012
url	https://doaj.org/article/40d6f706fb004e53af57426628f8b27f
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Methylselenol formed by spontaneous methylation of selenide is a superior selenium substrate to the thioredoxin and glutaredoxin systems.

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