Cadmium induces transcription independently of intracellular calcium mobilization.

<h4>Background</h4>Exposure to cadmium is associated with human pathologies and altered gene expression. The molecular mechanisms by which cadmium affects transcription remain unclear. It has been proposed that cadmium activates transcription by altering intracellular calcium concentrati...

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Autores principales:	Brooke E Tvermoes, Gary S Bird, Jonathan H Freedman
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2011
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/22c73d72eb0e4120b11030704808799d
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spelling	oai:doaj.org-article:22c73d72eb0e4120b11030704808799d2021-11-18T06:52:22ZCadmium induces transcription independently of intracellular calcium mobilization.1932-620310.1371/journal.pone.0020542https://doaj.org/article/22c73d72eb0e4120b11030704808799d2011-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/21694771/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Background</h4>Exposure to cadmium is associated with human pathologies and altered gene expression. The molecular mechanisms by which cadmium affects transcription remain unclear. It has been proposed that cadmium activates transcription by altering intracellular calcium concentration ([Ca(2+)](i)) and disrupting calcium-mediated intracellular signaling processes. This hypothesis is based on several studies that may be technically problematic; including the use of BAPTA chelators, BAPTA-based fluorescent sensors, and cytotoxic concentrations of metal.<h4>Methodology/principal finding</h4>In the present report, the effects of cadmium on [Ca(2+)](i) under non-cytotoxic and cytotoxic conditions was monitored using the protein-based calcium sensor yellow cameleon (YC3.60), which was stably expressed in HEK293 cells. In HEK293 constitutively expressing YC3.60, this calcium sensor was found to be insensitive to cadmium. Exposing HEK293::YC3.60 cells to non-cytotoxic cadmium concentrations was sufficient to induce transcription of cadmium-responsive genes but did not affect [Ca(2+)](i) mobilization or increase steady-state mRNA levels of calcium-responsive genes. In contrast, exposure to cytotoxic concentrations of cadmium significantly reduced intracellular calcium stores and altered calcium-responsive gene expression.<h4>Conclusions/significance</h4>These data indicate that at low levels, cadmium induces transcription independently of intracellular calcium mobilization. The results also support a model whereby cytotoxic levels of cadmium activate calcium-responsive transcription as a general response to metal-induced intracellular damage and not via a specific mechanism. Thus, the modulation of intracellular calcium may not be a primary mechanism by which cadmium regulates transcription.Brooke E TvermoesGary S BirdJonathan H FreedmanPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 6, Iss 6, p e20542 (2011)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Brooke E Tvermoes Gary S Bird Jonathan H Freedman Cadmium induces transcription independently of intracellular calcium mobilization.
description	<h4>Background</h4>Exposure to cadmium is associated with human pathologies and altered gene expression. The molecular mechanisms by which cadmium affects transcription remain unclear. It has been proposed that cadmium activates transcription by altering intracellular calcium concentration ([Ca(2+)](i)) and disrupting calcium-mediated intracellular signaling processes. This hypothesis is based on several studies that may be technically problematic; including the use of BAPTA chelators, BAPTA-based fluorescent sensors, and cytotoxic concentrations of metal.<h4>Methodology/principal finding</h4>In the present report, the effects of cadmium on [Ca(2+)](i) under non-cytotoxic and cytotoxic conditions was monitored using the protein-based calcium sensor yellow cameleon (YC3.60), which was stably expressed in HEK293 cells. In HEK293 constitutively expressing YC3.60, this calcium sensor was found to be insensitive to cadmium. Exposing HEK293::YC3.60 cells to non-cytotoxic cadmium concentrations was sufficient to induce transcription of cadmium-responsive genes but did not affect [Ca(2+)](i) mobilization or increase steady-state mRNA levels of calcium-responsive genes. In contrast, exposure to cytotoxic concentrations of cadmium significantly reduced intracellular calcium stores and altered calcium-responsive gene expression.<h4>Conclusions/significance</h4>These data indicate that at low levels, cadmium induces transcription independently of intracellular calcium mobilization. The results also support a model whereby cytotoxic levels of cadmium activate calcium-responsive transcription as a general response to metal-induced intracellular damage and not via a specific mechanism. Thus, the modulation of intracellular calcium may not be a primary mechanism by which cadmium regulates transcription.
format	article
author	Brooke E Tvermoes Gary S Bird Jonathan H Freedman
author_facet	Brooke E Tvermoes Gary S Bird Jonathan H Freedman
author_sort	Brooke E Tvermoes
title	Cadmium induces transcription independently of intracellular calcium mobilization.
title_short	Cadmium induces transcription independently of intracellular calcium mobilization.
title_full	Cadmium induces transcription independently of intracellular calcium mobilization.
title_fullStr	Cadmium induces transcription independently of intracellular calcium mobilization.
title_full_unstemmed	Cadmium induces transcription independently of intracellular calcium mobilization.
title_sort	cadmium induces transcription independently of intracellular calcium mobilization.
publisher	Public Library of Science (PLoS)
publishDate	2011
url	https://doaj.org/article/22c73d72eb0e4120b11030704808799d
work_keys_str_mv	AT brookeetvermoes cadmiuminducestranscriptionindependentlyofintracellularcalciummobilization AT garysbird cadmiuminducestranscriptionindependentlyofintracellularcalciummobilization AT jonathanhfreedman cadmiuminducestranscriptionindependentlyofintracellularcalciummobilization
_version_	1718424278834085888

Cadmium induces transcription independently of intracellular calcium mobilization.

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