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

Cite this

@article{bfd0b3b749df4b698f20dcda9db14b57,
title = "Endothelin-1- and depolarization-induced differential regulation of cAMP response element-binding protein in proliferating and developed vascular smooth muscle",
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.",
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",
author = "Egan, {Colin Gerard} and Nixon, {Graeme Fleming}",
year = "2004",
doi = "10.1016/j.cellsig.2004.04.008",
language = "English",
volume = "16",
pages = "1387--1396",
journal = "Cellular Signalling",
issn = "0898-6568",
publisher = "Elsevier Inc.",
number = "12",

}

TY - JOUR

T1 - Endothelin-1- and depolarization-induced differential regulation of cAMP response element-binding protein in proliferating and developed vascular smooth muscle

AU - Egan, Colin Gerard

AU - Nixon, Graeme Fleming

PY - 2004

Y1 - 2004

N2 - 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.

AB - 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.

KW - vascular smooth muscle

KW - cAMP response element-binding protein

KW - endothelin-1

KW - calcium

KW - calmodulin-dependent protein kinase

KW - GENE-EXPRESSION

KW - MEMBRANE DEPOLARIZATION

KW - CEREBRAL-ARTERIES

KW - CREB ACTIVATION

KW - CELLS

KW - KINASE

KW - PHOSPHORYLATION

KW - CA2+

KW - RAT

KW - TRANSCRIPTION

U2 - 10.1016/j.cellsig.2004.04.008

DO - 10.1016/j.cellsig.2004.04.008

M3 - Article

VL - 16

SP - 1387

EP - 1396

JO - Cellular Signalling

JF - Cellular Signalling

SN - 0898-6568

IS - 12

ER -