Endothelin-1- and depolarization-induced differential regulation of cAMP response element-binding protein in proliferating and developed vascular smooth muscle

Colin Gerard Egan, Graeme Fleming Nixon

Research output: Contribution to journalArticle

11 Citations (Scopus)

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 languageEnglish
Pages (from-to)1387-1396
Number of pages9
JournalCellular Signalling
Volume16
Issue number12
DOIs
Publication statusPublished - 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

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