Am J Physiol Heart Circ Physiol 2006,
PMID: 16461377
Pulver-Kaste, Renee A; Barlow, Christy A; Bond, Jeffery; Watson, Anjanette; Penar, Paul L; Tranmer, Bruce; Lounsbury, Karen M
Altered Ca2+ handling has immediate physiological and long-term genomic effects on vascular smooth muscle function. Previously we showed that Ca2+ entry through voltage-dependent Ca2+ channels (VDCCs) or store-operated Ca2+ channels (SOCCs) results in phosphorylation of the Ca2+/cAMP response element (CRE)-binding protein in cerebral arteries. Here, oligonucleotide array analysis was used to determine gene transcription profiles resulting from these two Ca2+ 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+ 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 Ca2+ entry through VDCCs and store-operated Ca2+ 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 Ca2+.
Diseases/Pathways annotated by Medline MESH: Calcium Signaling
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Text Mining Data
MKP-1 → ANG II: "
The physiological agonist
ANG II also
stimulated expression of Egr-1 and
MKP-1
"
Egr-1 → ANG II: "
The physiological agonist ANG II also stimulated expression of Egr-1 and MKP-1
"
ERK → ANG II: "
TG and ANG II induced phosphorylation of ERK , which was sensitive to 2-APB and was selectively required for CRE binding protein phosphorylation
"
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