Abstract
Regulation of the transcription factor cAMP response element-binding protein (CREB) is important for gene expression in vascular smooth muscle (VSM). This study has examined the intracellular regulation of CREB by endothelin-1 (ET-1) and depolarization in native VSM, comparing proliferative and fully differentiated phenotypes. Portal veins from neonatal (proliferative) and 6-week-old (differentiated) rats were stimulated with ET-1 or K+. In both phenotypes, CREB activation was increased by ET-1 although the time course was prolonged in neonatal VSM. This paralleled a prolonged ET-1-induced [Ca2+](i) increase. ET-1-induced CREB activation was dependent on extracellular signal-regulated kinase 1/2 (ERK1/2) activation and inhibited by BAPTA but not by a calmodulin-dependent protein kinase (CamK) inhibitor. In contrast, CREB activation induced by depolarization in both neonatal and developed VSM was significantly reduced by CaMK inhibition and by ERK1/2 inhibition. Therefore, CREB activation is regulated differentially in VSM depending upon stimulus; however, this is not altered in different growth states. (C) 2004 Elsevier Inc. All rights reserved.
Original language | English |
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Pages (from-to) | 1387-1396 |
Number of pages | 9 |
Journal | Cellular Signalling |
Volume | 16 |
Issue number | 12 |
DOIs | |
Publication status | Published - 2004 |
Keywords
- vascular smooth muscle
- cAMP response element-binding protein
- endothelin-1
- calcium
- calmodulin-dependent protein kinase
- GENE-EXPRESSION
- MEMBRANE DEPOLARIZATION
- CEREBRAL-ARTERIES
- CREB ACTIVATION
- CELLS
- KINASE
- PHOSPHORYLATION
- CA2+
- RAT
- TRANSCRIPTION