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Sulfheme formation during homocysteine S-oxygenation by catalase in cancers and neurodegenerative diseases

Accumulating evidence suggests that abnormal levels of homocysteine are associated with vascular dysfunctions, cancer cell proliferation and various neurodegenerative diseases. With respect to the latter, a perturbation of transition metal homeostasis and an inhibition of catalase bioactivity have b...

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Autores principales: Padovani, Dominique, Hessani, Assia, Castillo, Francine T., Liot, Géraldine, Andriamihaja, Mireille, Lan, Annaïg, Pilati, Camilla, Blachier, François, Sen, Suvajit, Galardon, Erwan, Artaud, Isabelle
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5116089/
https://www.ncbi.nlm.nih.gov/pubmed/27848965
http://dx.doi.org/10.1038/ncomms13386
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author Padovani, Dominique
Hessani, Assia
Castillo, Francine T.
Liot, Géraldine
Andriamihaja, Mireille
Lan, Annaïg
Pilati, Camilla
Blachier, François
Sen, Suvajit
Galardon, Erwan
Artaud, Isabelle
author_facet Padovani, Dominique
Hessani, Assia
Castillo, Francine T.
Liot, Géraldine
Andriamihaja, Mireille
Lan, Annaïg
Pilati, Camilla
Blachier, François
Sen, Suvajit
Galardon, Erwan
Artaud, Isabelle
author_sort Padovani, Dominique
collection PubMed
description Accumulating evidence suggests that abnormal levels of homocysteine are associated with vascular dysfunctions, cancer cell proliferation and various neurodegenerative diseases. With respect to the latter, a perturbation of transition metal homeostasis and an inhibition of catalase bioactivity have been reported. Herein, we report on some of the molecular bases for the cellular toxicity of homocysteine and demonstrate that it induces the formation of sulfcatalase, an irreversible inactive state of the enzyme, without the intervention of hydrogen sulfide. Initially, homocysteine reacts with native catalase and/or redox-active transition metal ions to generate thiyl radicals that mediate compound II formation, a temporarily inactive state of the enzyme. Then, the ferryl centre of compound II intervenes into the unprecedented S-oxygenation of homocysteine to engender the corresponding sulfenic acid species that further participates into the prosthetic heme modification through the formation of an unusual Fe(II) sulfonium. In addition, our ex cellulo studies performed on cancer cells, models of neurodegenerative diseases and ulcerative colitis suggest the likelihood of this scenario in a subset of cancer cells, as well as in a cellular model of Parkinson's disease. Our findings expand the repertoire of heme modifications promoted by biological compounds and point out another deleterious trait of disturbed homocysteine levels that could participate in the aetiology of these diseases.
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spelling pubmed-51160892017-01-13 Sulfheme formation during homocysteine S-oxygenation by catalase in cancers and neurodegenerative diseases Padovani, Dominique Hessani, Assia Castillo, Francine T. Liot, Géraldine Andriamihaja, Mireille Lan, Annaïg Pilati, Camilla Blachier, François Sen, Suvajit Galardon, Erwan Artaud, Isabelle Nat Commun Article Accumulating evidence suggests that abnormal levels of homocysteine are associated with vascular dysfunctions, cancer cell proliferation and various neurodegenerative diseases. With respect to the latter, a perturbation of transition metal homeostasis and an inhibition of catalase bioactivity have been reported. Herein, we report on some of the molecular bases for the cellular toxicity of homocysteine and demonstrate that it induces the formation of sulfcatalase, an irreversible inactive state of the enzyme, without the intervention of hydrogen sulfide. Initially, homocysteine reacts with native catalase and/or redox-active transition metal ions to generate thiyl radicals that mediate compound II formation, a temporarily inactive state of the enzyme. Then, the ferryl centre of compound II intervenes into the unprecedented S-oxygenation of homocysteine to engender the corresponding sulfenic acid species that further participates into the prosthetic heme modification through the formation of an unusual Fe(II) sulfonium. In addition, our ex cellulo studies performed on cancer cells, models of neurodegenerative diseases and ulcerative colitis suggest the likelihood of this scenario in a subset of cancer cells, as well as in a cellular model of Parkinson's disease. Our findings expand the repertoire of heme modifications promoted by biological compounds and point out another deleterious trait of disturbed homocysteine levels that could participate in the aetiology of these diseases. Nature Publishing Group 2016-11-16 /pmc/articles/PMC5116089/ /pubmed/27848965 http://dx.doi.org/10.1038/ncomms13386 Text en Copyright © 2016, The Author(s) http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
spellingShingle Article
Padovani, Dominique
Hessani, Assia
Castillo, Francine T.
Liot, Géraldine
Andriamihaja, Mireille
Lan, Annaïg
Pilati, Camilla
Blachier, François
Sen, Suvajit
Galardon, Erwan
Artaud, Isabelle
Sulfheme formation during homocysteine S-oxygenation by catalase in cancers and neurodegenerative diseases
title Sulfheme formation during homocysteine S-oxygenation by catalase in cancers and neurodegenerative diseases
title_full Sulfheme formation during homocysteine S-oxygenation by catalase in cancers and neurodegenerative diseases
title_fullStr Sulfheme formation during homocysteine S-oxygenation by catalase in cancers and neurodegenerative diseases
title_full_unstemmed Sulfheme formation during homocysteine S-oxygenation by catalase in cancers and neurodegenerative diseases
title_short Sulfheme formation during homocysteine S-oxygenation by catalase in cancers and neurodegenerative diseases
title_sort sulfheme formation during homocysteine s-oxygenation by catalase in cancers and neurodegenerative diseases
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5116089/
https://www.ncbi.nlm.nih.gov/pubmed/27848965
http://dx.doi.org/10.1038/ncomms13386
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