Ca^sup 2+^ source-dependent transcription of CRE-containing genes in vascular smooth muscle

Altered Ca^sup 2+^ handling has immediate physiological and long-term genomic effects on vascular smooth muscle function. Previously we showed that Ca^sup 2+^ entry through voltage-dependent Ca^sup 2+^ channels (VDCCs) or store-operated Ca^sup 2+^ channels (SOCCs) results in phosphorylation of the C...

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Bibliographic Details
Published in:American journal of physiology. Heart and circulatory physiology 2006-07, Vol.291 (1), p.38
Main Authors: Pulver-Kaste, Renee A, Barlow, Christy A, Bond, Jeffery, Watson, Anjanette
Format: Article
Language:English
Subjects:
Calcium
Cardiovascular system
Circulatory system
Genes
Genomics
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Summary:Altered Ca^sup 2+^ handling has immediate physiological and long-term genomic effects on vascular smooth muscle function. Previously we showed that Ca^sup 2+^ entry through voltage-dependent Ca^sup 2+^ channels (VDCCs) or store-operated Ca^sup 2+^ channels (SOCCs) results in phosphorylation of the Ca^sup 2+^/cAMP response element (CRE)-binding protein in cerebral arteries. Here, oligonucleotide array analysis was used to determine gene transcription profiles resulting from these two Ca^sup 2+^ entry pathways in human cerebrovascular smooth muscle cell cultures. Results were confirmed and expanded using quantitative RT-PCR, Western blot, and immunofluorescence. A distinct, yet overlapping, set of CRE-regulated genes was induced by VDCC activation using K^sup +^ membrane depolarization vs. SOCC activation by thapsigargin (TG). Membrane depolarization selectively induced a sustained increase in early growth response-1 (Egr- 1) mRNA and protein, which were inhibited by the VDCC blocker nimodipine and the SOCC inhibitor 2-aminoethoxydiphenylborate (2-APB). TG selectively induced a sustained increase in MAPK phosphatase-1 (MKP-1) mRNA and protein, and these effects were decreased by 2-APB, but not by nimodipine. The physiological agonist ANG II also stimulated expression of Egr-1 and MKP-1. Coadministration of 2-APB prevented expression of Egr-1 and MKP-1, whereas nimodipine blocked only Egr-1 expression. TG and ANG II induced phosphorylation of ERK, which was sensitive to 2-APB and was selectively required for CRE-binding protein phosphorylation. Our findings thus indicate that Ca^sup 2+^ entry through VDCCs and store-operated Ca^sup 2+^ entry can differentially regulate CRE-containing genes in vascular smooth muscle and also imply that agonist-induced signals involved in modulation of gene transcription can be controlled by multiple sources of Ca^sup 2+^. [PUBLICATION ABSTRACT]
ISSN:0363-6135
1522-1539