Biosensors paving the way to understanding the interaction between cadmium and the estrogen receptor alpha.

Cadmium is a toxic heavy metal ubiquitously present in the environment and subsequently in the human diet. Cadmium has been proposed to disrupt the endocrine system, targeting in particular the estrogen signaling pathway already at environmentally relevant concentrations. Thus far, the reports on th...

Descripción completa

Guardado en:
Detalles Bibliográficos
Autores principales: Peter Fechner, Pauliina Damdimopoulou, Günter Gauglitz
Formato: article
Lenguaje:EN
Publicado: Public Library of Science (PLoS) 2011
Materias:
R
Q
Acceso en línea:https://doaj.org/article/c9a8f6a4173240b7ac642e3b3679d146
Etiquetas: Agregar Etiqueta
Sin Etiquetas, Sea el primero en etiquetar este registro!
id oai:doaj.org-article:c9a8f6a4173240b7ac642e3b3679d146
record_format dspace
spelling oai:doaj.org-article:c9a8f6a4173240b7ac642e3b3679d1462021-11-18T06:48:50ZBiosensors paving the way to understanding the interaction between cadmium and the estrogen receptor alpha.1932-620310.1371/journal.pone.0023048https://doaj.org/article/c9a8f6a4173240b7ac642e3b3679d1462011-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/21829690/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203Cadmium is a toxic heavy metal ubiquitously present in the environment and subsequently in the human diet. Cadmium has been proposed to disrupt the endocrine system, targeting in particular the estrogen signaling pathway already at environmentally relevant concentrations. Thus far, the reports on the binding affinity of cadmium towards human estrogen receptor alpha (hERα) have been contradicting, as have been the reports on the in vivo estrogenicity of cadmium. Hence, the mode of interaction between cadmium and the receptor remains unclear. Here, we investigated the interaction between cadmium and hERα on a molecular level by applying a novel, label-free biosensor technique based on reflectometric interference spectroscopy (RIfS). We studied the binding of cadmium to hERα, and the conformation of the receptor following cadmium treatment. Our data reveals that cadmium interacts with the ligand binding domain (LBD) of the ERα and affects the conformation of the receptor. However, the binding event, as well as the induced conformation change, greatly depends on the accessibility of the cysteine tails in the LBD. As the LBD cysteine residues have been reported as targets of post-translational modifications in vivo, we present a hypothesis according to which different cellular pools of ERα respond to cadmium differently. Our proposed theory could help to explain some of the previously contradicting results regarding estrogen-like activity of cadmium.Peter FechnerPauliina DamdimopoulouGünter GauglitzPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 6, Iss 8, p e23048 (2011)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Peter Fechner
Pauliina Damdimopoulou
Günter Gauglitz
Biosensors paving the way to understanding the interaction between cadmium and the estrogen receptor alpha.
description Cadmium is a toxic heavy metal ubiquitously present in the environment and subsequently in the human diet. Cadmium has been proposed to disrupt the endocrine system, targeting in particular the estrogen signaling pathway already at environmentally relevant concentrations. Thus far, the reports on the binding affinity of cadmium towards human estrogen receptor alpha (hERα) have been contradicting, as have been the reports on the in vivo estrogenicity of cadmium. Hence, the mode of interaction between cadmium and the receptor remains unclear. Here, we investigated the interaction between cadmium and hERα on a molecular level by applying a novel, label-free biosensor technique based on reflectometric interference spectroscopy (RIfS). We studied the binding of cadmium to hERα, and the conformation of the receptor following cadmium treatment. Our data reveals that cadmium interacts with the ligand binding domain (LBD) of the ERα and affects the conformation of the receptor. However, the binding event, as well as the induced conformation change, greatly depends on the accessibility of the cysteine tails in the LBD. As the LBD cysteine residues have been reported as targets of post-translational modifications in vivo, we present a hypothesis according to which different cellular pools of ERα respond to cadmium differently. Our proposed theory could help to explain some of the previously contradicting results regarding estrogen-like activity of cadmium.
format article
author Peter Fechner
Pauliina Damdimopoulou
Günter Gauglitz
author_facet Peter Fechner
Pauliina Damdimopoulou
Günter Gauglitz
author_sort Peter Fechner
title Biosensors paving the way to understanding the interaction between cadmium and the estrogen receptor alpha.
title_short Biosensors paving the way to understanding the interaction between cadmium and the estrogen receptor alpha.
title_full Biosensors paving the way to understanding the interaction between cadmium and the estrogen receptor alpha.
title_fullStr Biosensors paving the way to understanding the interaction between cadmium and the estrogen receptor alpha.
title_full_unstemmed Biosensors paving the way to understanding the interaction between cadmium and the estrogen receptor alpha.
title_sort biosensors paving the way to understanding the interaction between cadmium and the estrogen receptor alpha.
publisher Public Library of Science (PLoS)
publishDate 2011
url https://doaj.org/article/c9a8f6a4173240b7ac642e3b3679d146
work_keys_str_mv AT peterfechner biosensorspavingthewaytounderstandingtheinteractionbetweencadmiumandtheestrogenreceptoralpha
AT pauliinadamdimopoulou biosensorspavingthewaytounderstandingtheinteractionbetweencadmiumandtheestrogenreceptoralpha
AT guntergauglitz biosensorspavingthewaytounderstandingtheinteractionbetweencadmiumandtheestrogenreceptoralpha
_version_ 1718424379336949760