Details

Autor(en) / Beteiligte

• Pulver-Kaste, Renee A.
• Barlow, Christy A.
• Bond, Jeffery
• Watson, Anjanette
• Penar, Paul L.
• Tranmer, Bruce
• Lounsbury, Karen M.

Titel

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

Ist Teil von

• American journal of physiology. Heart and circulatory physiology, 2006-07, Vol.291 (1), p.H97-H105

Erscheinungsjahr

2006

Quelle

Free E-Journal (出版社公開部分のみ）

Beschreibungen/Notizen

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