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Ubiquitous [Na(+)](i)/[K(+)](i)-Sensitive Transcriptome in Mammalian Cells: Evidence for Ca(2+) (i)-Independent Excitation-Transcription Coupling

Stimulus-dependent elevation of intracellular Ca(2+) ([Ca(2+)](i)) affects the expression of numerous genes – a phenomenon known as excitation-transcription coupling. Recently, we found that increases in [Na(+)](i) trigger c-Fos expression via a novel Ca(2+) (i)-independent pathway. In the present s...

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Autores principales: Koltsova, Svetlana V., Trushina, Yulia, Haloui, Mounsif, Akimova, Olga A., Tremblay, Johanne, Hamet, Pavel, Orlov, Sergei N.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3362528/
https://www.ncbi.nlm.nih.gov/pubmed/22666440
http://dx.doi.org/10.1371/journal.pone.0038032
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author Koltsova, Svetlana V.
Trushina, Yulia
Haloui, Mounsif
Akimova, Olga A.
Tremblay, Johanne
Hamet, Pavel
Orlov, Sergei N.
author_facet Koltsova, Svetlana V.
Trushina, Yulia
Haloui, Mounsif
Akimova, Olga A.
Tremblay, Johanne
Hamet, Pavel
Orlov, Sergei N.
author_sort Koltsova, Svetlana V.
collection PubMed
description Stimulus-dependent elevation of intracellular Ca(2+) ([Ca(2+)](i)) affects the expression of numerous genes – a phenomenon known as excitation-transcription coupling. Recently, we found that increases in [Na(+)](i) trigger c-Fos expression via a novel Ca(2+) (i)-independent pathway. In the present study, we identified ubiquitous and tissue-specific [Na(+)](i)/[K(+)](i)-sensitive transcriptomes by comparative analysis of differentially expressed genes in vascular smooth muscle cells from rat aorta (RVSMC), the human adenocarcinoma cell line HeLa, and human umbilical vein endothelial cells (HUVEC). To augment [Na(+)](i) and reduce [K(+)](i), cells were treated for 3 hrs with the Na(+),K(+)-ATPase inhibitor ouabain or placed for the same time in the K(+)-free medium. Employing Affymetrix-based technology, we detected changes in expression levels of 684, 737 and 1839 transcripts in HeLa, HUVEC and RVSMC, respectively, that were highly correlated between two treatments (p<0.0001; R(2)>0.62). Among these Na(+) (i)/K(+) (i)-sensitive genes, 80 transcripts were common for all three types of cells. To establish if changes in gene expression are dependent on increases in [Ca(2+)](i), we performed identical experiments in Ca(2+)-free media supplemented with extracellular and intracellular Ca(2+) chelators. Surprisingly, this procedure elevated rather than decreased the number of ubiquitous and cell-type specific Na(+) (i)/K(+) (i)-sensitive genes. Among the ubiquitous Na(+) (i)/K(+) (i)-sensitive genes whose expression was regulated independently of the presence of Ca(2+) chelators by more than 3-fold, we discovered several transcription factors (Fos, Jun, Hes1, Nfkbia), interleukin-6, protein phosphatase 1 regulatory subunit, dual specificity phosphatase (Dusp8), prostaglandin-endoperoxide synthase 2, cyclin L1, whereas expression of metallopeptidase Adamts1, adrenomedulin, Dups1, Dusp10 and Dusp16 was detected exclusively in Ca(2+)-depleted cells. Overall, our findings indicate that Ca(2+) (i)-independent mechanisms of excitation-transcription coupling are involved in transcriptomic alterations triggered by elevation of the [Na(+)](i)/[K(+)](i) ratio. There results likely have profound implications for normal and pathological regulation of mammalian cells, including sustained excitation of neuronal cells, intensive exercise and ischemia-triggered disorders.
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spelling pubmed-33625282012-06-04 Ubiquitous [Na(+)](i)/[K(+)](i)-Sensitive Transcriptome in Mammalian Cells: Evidence for Ca(2+) (i)-Independent Excitation-Transcription Coupling Koltsova, Svetlana V. Trushina, Yulia Haloui, Mounsif Akimova, Olga A. Tremblay, Johanne Hamet, Pavel Orlov, Sergei N. PLoS One Research Article Stimulus-dependent elevation of intracellular Ca(2+) ([Ca(2+)](i)) affects the expression of numerous genes – a phenomenon known as excitation-transcription coupling. Recently, we found that increases in [Na(+)](i) trigger c-Fos expression via a novel Ca(2+) (i)-independent pathway. In the present study, we identified ubiquitous and tissue-specific [Na(+)](i)/[K(+)](i)-sensitive transcriptomes by comparative analysis of differentially expressed genes in vascular smooth muscle cells from rat aorta (RVSMC), the human adenocarcinoma cell line HeLa, and human umbilical vein endothelial cells (HUVEC). To augment [Na(+)](i) and reduce [K(+)](i), cells were treated for 3 hrs with the Na(+),K(+)-ATPase inhibitor ouabain or placed for the same time in the K(+)-free medium. Employing Affymetrix-based technology, we detected changes in expression levels of 684, 737 and 1839 transcripts in HeLa, HUVEC and RVSMC, respectively, that were highly correlated between two treatments (p<0.0001; R(2)>0.62). Among these Na(+) (i)/K(+) (i)-sensitive genes, 80 transcripts were common for all three types of cells. To establish if changes in gene expression are dependent on increases in [Ca(2+)](i), we performed identical experiments in Ca(2+)-free media supplemented with extracellular and intracellular Ca(2+) chelators. Surprisingly, this procedure elevated rather than decreased the number of ubiquitous and cell-type specific Na(+) (i)/K(+) (i)-sensitive genes. Among the ubiquitous Na(+) (i)/K(+) (i)-sensitive genes whose expression was regulated independently of the presence of Ca(2+) chelators by more than 3-fold, we discovered several transcription factors (Fos, Jun, Hes1, Nfkbia), interleukin-6, protein phosphatase 1 regulatory subunit, dual specificity phosphatase (Dusp8), prostaglandin-endoperoxide synthase 2, cyclin L1, whereas expression of metallopeptidase Adamts1, adrenomedulin, Dups1, Dusp10 and Dusp16 was detected exclusively in Ca(2+)-depleted cells. Overall, our findings indicate that Ca(2+) (i)-independent mechanisms of excitation-transcription coupling are involved in transcriptomic alterations triggered by elevation of the [Na(+)](i)/[K(+)](i) ratio. There results likely have profound implications for normal and pathological regulation of mammalian cells, including sustained excitation of neuronal cells, intensive exercise and ischemia-triggered disorders. Public Library of Science 2012-05-29 /pmc/articles/PMC3362528/ /pubmed/22666440 http://dx.doi.org/10.1371/journal.pone.0038032 Text en Koltsova et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Koltsova, Svetlana V.
Trushina, Yulia
Haloui, Mounsif
Akimova, Olga A.
Tremblay, Johanne
Hamet, Pavel
Orlov, Sergei N.
Ubiquitous [Na(+)](i)/[K(+)](i)-Sensitive Transcriptome in Mammalian Cells: Evidence for Ca(2+) (i)-Independent Excitation-Transcription Coupling
title Ubiquitous [Na(+)](i)/[K(+)](i)-Sensitive Transcriptome in Mammalian Cells: Evidence for Ca(2+) (i)-Independent Excitation-Transcription Coupling
title_full Ubiquitous [Na(+)](i)/[K(+)](i)-Sensitive Transcriptome in Mammalian Cells: Evidence for Ca(2+) (i)-Independent Excitation-Transcription Coupling
title_fullStr Ubiquitous [Na(+)](i)/[K(+)](i)-Sensitive Transcriptome in Mammalian Cells: Evidence for Ca(2+) (i)-Independent Excitation-Transcription Coupling
title_full_unstemmed Ubiquitous [Na(+)](i)/[K(+)](i)-Sensitive Transcriptome in Mammalian Cells: Evidence for Ca(2+) (i)-Independent Excitation-Transcription Coupling
title_short Ubiquitous [Na(+)](i)/[K(+)](i)-Sensitive Transcriptome in Mammalian Cells: Evidence for Ca(2+) (i)-Independent Excitation-Transcription Coupling
title_sort ubiquitous [na(+)](i)/[k(+)](i)-sensitive transcriptome in mammalian cells: evidence for ca(2+) (i)-independent excitation-transcription coupling
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3362528/
https://www.ncbi.nlm.nih.gov/pubmed/22666440
http://dx.doi.org/10.1371/journal.pone.0038032
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