Cargando…

RhoA-ROCK signaling is involved in contraction-mediated inhibition of SERCA2a expression in cardiomyocytes

In neonatal ventricular cardiomyocytes (NVCM), decreased contractile activity stimulates sarco-endoplasmic reticulum Ca(2+)-ATPase2a (SERCA2a), analogous to reduced myocardial load in vivo. This study investigated in contracting NVCM the role of load-dependent RhoA-ROCK signaling in SERCA2a regulati...

Descripción completa

Detalles Bibliográficos
Autores principales: Vlasblom, Ronald, Muller, Alice, Beckers, Cora M. L., van Nieuw Amerongen, Geerten P., Zuidwijk, Marian J., van Hardeveld, Cornelis, Paulus, Walter J., Simonides, Warner S.
Formato: Texto
Lenguaje:English
Publicado: Springer-Verlag 2009
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2704291/
https://www.ncbi.nlm.nih.gov/pubmed/19294414
http://dx.doi.org/10.1007/s00424-009-0659-x
_version_ 1782168923849883648
author Vlasblom, Ronald
Muller, Alice
Beckers, Cora M. L.
van Nieuw Amerongen, Geerten P.
Zuidwijk, Marian J.
van Hardeveld, Cornelis
Paulus, Walter J.
Simonides, Warner S.
author_facet Vlasblom, Ronald
Muller, Alice
Beckers, Cora M. L.
van Nieuw Amerongen, Geerten P.
Zuidwijk, Marian J.
van Hardeveld, Cornelis
Paulus, Walter J.
Simonides, Warner S.
author_sort Vlasblom, Ronald
collection PubMed
description In neonatal ventricular cardiomyocytes (NVCM), decreased contractile activity stimulates sarco-endoplasmic reticulum Ca(2+)-ATPase2a (SERCA2a), analogous to reduced myocardial load in vivo. This study investigated in contracting NVCM the role of load-dependent RhoA-ROCK signaling in SERCA2a regulation. Contractile arrest of NVCM resulted in low peri-nuclear localized RhoA levels relative to contracting NVCM. In arrested NVCM, ROCK activity was decreased (59%) and paralleled a loss in F-actin levels. Y-27632-induced ROCK inhibition in contracting NVCM increased SERCA2a messenger RNA expression by 150%. This stimulation was transcriptional, as evident from transfections with the SERCA2a promoter. A reciprocal effect of Y-27632 treatment on the promoter activity of atrial natriuretic factor was observed. SERCA2a transcription was not altered by co-transfection of the RhoA-ROCK-dependent serum response factor (SRF) alone or in combination with myocardin. Furthermore, GATA4, another ROCK-dependent transcription factor, induced rather than repressed SERCA2a transcription. This study shows that contractile activity suppresses SERCA2a gene expression via RhoA-ROCK-dependent transcription modulation. This modulation is likely to be accomplished by a transcription factor other than SRF, myocardin, or GATA4.
format Text
id pubmed-2704291
institution National Center for Biotechnology Information
language English
publishDate 2009
publisher Springer-Verlag
record_format MEDLINE/PubMed
spelling pubmed-27042912009-07-01 RhoA-ROCK signaling is involved in contraction-mediated inhibition of SERCA2a expression in cardiomyocytes Vlasblom, Ronald Muller, Alice Beckers, Cora M. L. van Nieuw Amerongen, Geerten P. Zuidwijk, Marian J. van Hardeveld, Cornelis Paulus, Walter J. Simonides, Warner S. Pflugers Arch Signaling and Cell Physiology In neonatal ventricular cardiomyocytes (NVCM), decreased contractile activity stimulates sarco-endoplasmic reticulum Ca(2+)-ATPase2a (SERCA2a), analogous to reduced myocardial load in vivo. This study investigated in contracting NVCM the role of load-dependent RhoA-ROCK signaling in SERCA2a regulation. Contractile arrest of NVCM resulted in low peri-nuclear localized RhoA levels relative to contracting NVCM. In arrested NVCM, ROCK activity was decreased (59%) and paralleled a loss in F-actin levels. Y-27632-induced ROCK inhibition in contracting NVCM increased SERCA2a messenger RNA expression by 150%. This stimulation was transcriptional, as evident from transfections with the SERCA2a promoter. A reciprocal effect of Y-27632 treatment on the promoter activity of atrial natriuretic factor was observed. SERCA2a transcription was not altered by co-transfection of the RhoA-ROCK-dependent serum response factor (SRF) alone or in combination with myocardin. Furthermore, GATA4, another ROCK-dependent transcription factor, induced rather than repressed SERCA2a transcription. This study shows that contractile activity suppresses SERCA2a gene expression via RhoA-ROCK-dependent transcription modulation. This modulation is likely to be accomplished by a transcription factor other than SRF, myocardin, or GATA4. Springer-Verlag 2009-03-18 2009-08 /pmc/articles/PMC2704291/ /pubmed/19294414 http://dx.doi.org/10.1007/s00424-009-0659-x Text en © The Author(s) 2009
spellingShingle Signaling and Cell Physiology
Vlasblom, Ronald
Muller, Alice
Beckers, Cora M. L.
van Nieuw Amerongen, Geerten P.
Zuidwijk, Marian J.
van Hardeveld, Cornelis
Paulus, Walter J.
Simonides, Warner S.
RhoA-ROCK signaling is involved in contraction-mediated inhibition of SERCA2a expression in cardiomyocytes
title RhoA-ROCK signaling is involved in contraction-mediated inhibition of SERCA2a expression in cardiomyocytes
title_full RhoA-ROCK signaling is involved in contraction-mediated inhibition of SERCA2a expression in cardiomyocytes
title_fullStr RhoA-ROCK signaling is involved in contraction-mediated inhibition of SERCA2a expression in cardiomyocytes
title_full_unstemmed RhoA-ROCK signaling is involved in contraction-mediated inhibition of SERCA2a expression in cardiomyocytes
title_short RhoA-ROCK signaling is involved in contraction-mediated inhibition of SERCA2a expression in cardiomyocytes
title_sort rhoa-rock signaling is involved in contraction-mediated inhibition of serca2a expression in cardiomyocytes
topic Signaling and Cell Physiology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2704291/
https://www.ncbi.nlm.nih.gov/pubmed/19294414
http://dx.doi.org/10.1007/s00424-009-0659-x
work_keys_str_mv AT vlasblomronald rhoarocksignalingisinvolvedincontractionmediatedinhibitionofserca2aexpressionincardiomyocytes
AT mulleralice rhoarocksignalingisinvolvedincontractionmediatedinhibitionofserca2aexpressionincardiomyocytes
AT beckerscoraml rhoarocksignalingisinvolvedincontractionmediatedinhibitionofserca2aexpressionincardiomyocytes
AT vannieuwamerongengeertenp rhoarocksignalingisinvolvedincontractionmediatedinhibitionofserca2aexpressionincardiomyocytes
AT zuidwijkmarianj rhoarocksignalingisinvolvedincontractionmediatedinhibitionofserca2aexpressionincardiomyocytes
AT vanhardeveldcornelis rhoarocksignalingisinvolvedincontractionmediatedinhibitionofserca2aexpressionincardiomyocytes
AT pauluswalterj rhoarocksignalingisinvolvedincontractionmediatedinhibitionofserca2aexpressionincardiomyocytes
AT simonideswarners rhoarocksignalingisinvolvedincontractionmediatedinhibitionofserca2aexpressionincardiomyocytes