Sphingosine 1-phosphate induces CREB activation in rat cerebral artery via a protein kinase C-mediated inhibition of voltage-gated K+ channels

Frederic Coussin, Roderick Hamilton Scott, Graeme Fleming Nixon

Research output: Contribution to journalArticle

25 Citations (Scopus)

Abstract

Sphingosine 1-phosphate (SIP) is a potential mitogenic stimulus for vascular smooth muscle. S1P promotes an increase in the intracellular calcium concentration ([Ca2+](i)) in cerebral arteries, however S1P effects on regulation of gene expression are not known. Activation of the Ca2+-dependent transcription factor, cAMP response element-binding protein (CREB), is associated with smooth muscle proliferation. The aim of this study was to examine the Ca2+-dependent mechanisms involved in S1P-induced CREB activation in cerebral artery. Western blotting and immunofluorescence with a phospho-CREB antibody were used to detect CREB activation in Sprague-Dawley rat cerebral arteries. Whole-cell patch clamp recording and single cell imaging of [Ca2+]i were performed on freshly isolated cerebral artery myocytes. SIP increased activation of CREB in the nucleus of cerebral arteries. This activation was mediated by Ca2+/calmodulin-dependent protein kinase and was dependent on an increase in [Ca2+]i via two mechanisms: (i) intracellular Ca2+ release via an inositol 1,4,5-trisphosphate (InsP(3))-dependent pathway and (ii) Ca2+ entry through voltage-dependent Ca2+ channels (VDCC). Activation of the VDCC occurred through SIP-induced inhibition (approximately 50%) of the voltage-gated potassium (K+) current. This inhibition was via a protein kinase C-mediated pathway resulting in tyrosine phosphorylation of at least one isoform of the Kv channel (Kv 1.2). These results demonstrate that S1P can activate the transcription factor CREB through different Ca2+-dependent pathways including intracellular Ca2+ release and inhibition of voltage-gated K+ channels leading to Ca2+ influx. Our findings suggest a potential role for S1P in regulation of gene expression in vascular smooth muscle. (C) 2003 Elsevier Inc. All rights reserved.

Original languageEnglish
Pages (from-to)1861-1870
Number of pages9
JournalBiochemical Pharmacology
Volume66
Issue number9
DOIs
Publication statusPublished - 2003

Keywords

  • vascular smooth muscle
  • transcription factor
  • sphingosine 1-phosphate
  • calcium release
  • potassium channels
  • calcium channels
  • VASCULAR SMOOTH-MUSCLE
  • ELEMENT-BINDING PROTEIN
  • COUPLED RECEPTOR
  • GENE-EXPRESSION
  • INOSITOL 1,4,5-TRISPHOSPHATE
  • MEMBRANE DEPOLARIZATION
  • RYANODINE RECEPTORS
  • CELL-PROLIFERATION
  • MOLECULAR-CLONING
  • NUCLEAR-FACTOR

Cite this

Sphingosine 1-phosphate induces CREB activation in rat cerebral artery via a protein kinase C-mediated inhibition of voltage-gated K+ channels. / Coussin, Frederic; Scott, Roderick Hamilton; Nixon, Graeme Fleming.

In: Biochemical Pharmacology, Vol. 66, No. 9, 2003, p. 1861-1870.

Research output: Contribution to journalArticle

@article{51a0b4e3156f4e5d8d8b8d232ff4eb1f,
title = "Sphingosine 1-phosphate induces CREB activation in rat cerebral artery via a protein kinase C-mediated inhibition of voltage-gated K+ channels",
abstract = "Sphingosine 1-phosphate (SIP) is a potential mitogenic stimulus for vascular smooth muscle. S1P promotes an increase in the intracellular calcium concentration ([Ca2+](i)) in cerebral arteries, however S1P effects on regulation of gene expression are not known. Activation of the Ca2+-dependent transcription factor, cAMP response element-binding protein (CREB), is associated with smooth muscle proliferation. The aim of this study was to examine the Ca2+-dependent mechanisms involved in S1P-induced CREB activation in cerebral artery. Western blotting and immunofluorescence with a phospho-CREB antibody were used to detect CREB activation in Sprague-Dawley rat cerebral arteries. Whole-cell patch clamp recording and single cell imaging of [Ca2+]i were performed on freshly isolated cerebral artery myocytes. SIP increased activation of CREB in the nucleus of cerebral arteries. This activation was mediated by Ca2+/calmodulin-dependent protein kinase and was dependent on an increase in [Ca2+]i via two mechanisms: (i) intracellular Ca2+ release via an inositol 1,4,5-trisphosphate (InsP(3))-dependent pathway and (ii) Ca2+ entry through voltage-dependent Ca2+ channels (VDCC). Activation of the VDCC occurred through SIP-induced inhibition (approximately 50{\%}) of the voltage-gated potassium (K+) current. This inhibition was via a protein kinase C-mediated pathway resulting in tyrosine phosphorylation of at least one isoform of the Kv channel (Kv 1.2). These results demonstrate that S1P can activate the transcription factor CREB through different Ca2+-dependent pathways including intracellular Ca2+ release and inhibition of voltage-gated K+ channels leading to Ca2+ influx. Our findings suggest a potential role for S1P in regulation of gene expression in vascular smooth muscle. (C) 2003 Elsevier Inc. All rights reserved.",
keywords = "vascular smooth muscle, transcription factor, sphingosine 1-phosphate, calcium release, potassium channels, calcium channels, VASCULAR SMOOTH-MUSCLE, ELEMENT-BINDING PROTEIN, COUPLED RECEPTOR, GENE-EXPRESSION, INOSITOL 1,4,5-TRISPHOSPHATE, MEMBRANE DEPOLARIZATION, RYANODINE RECEPTORS, CELL-PROLIFERATION, MOLECULAR-CLONING, NUCLEAR-FACTOR",
author = "Frederic Coussin and Scott, {Roderick Hamilton} and Nixon, {Graeme Fleming}",
year = "2003",
doi = "10.1016/S0006-2952(03)00546-X",
language = "English",
volume = "66",
pages = "1861--1870",
journal = "Biochemical Pharmacology",
issn = "0006-2952",
publisher = "Elsevier Inc.",
number = "9",

}

TY - JOUR

T1 - Sphingosine 1-phosphate induces CREB activation in rat cerebral artery via a protein kinase C-mediated inhibition of voltage-gated K+ channels

AU - Coussin, Frederic

AU - Scott, Roderick Hamilton

AU - Nixon, Graeme Fleming

PY - 2003

Y1 - 2003

N2 - Sphingosine 1-phosphate (SIP) is a potential mitogenic stimulus for vascular smooth muscle. S1P promotes an increase in the intracellular calcium concentration ([Ca2+](i)) in cerebral arteries, however S1P effects on regulation of gene expression are not known. Activation of the Ca2+-dependent transcription factor, cAMP response element-binding protein (CREB), is associated with smooth muscle proliferation. The aim of this study was to examine the Ca2+-dependent mechanisms involved in S1P-induced CREB activation in cerebral artery. Western blotting and immunofluorescence with a phospho-CREB antibody were used to detect CREB activation in Sprague-Dawley rat cerebral arteries. Whole-cell patch clamp recording and single cell imaging of [Ca2+]i were performed on freshly isolated cerebral artery myocytes. SIP increased activation of CREB in the nucleus of cerebral arteries. This activation was mediated by Ca2+/calmodulin-dependent protein kinase and was dependent on an increase in [Ca2+]i via two mechanisms: (i) intracellular Ca2+ release via an inositol 1,4,5-trisphosphate (InsP(3))-dependent pathway and (ii) Ca2+ entry through voltage-dependent Ca2+ channels (VDCC). Activation of the VDCC occurred through SIP-induced inhibition (approximately 50%) of the voltage-gated potassium (K+) current. This inhibition was via a protein kinase C-mediated pathway resulting in tyrosine phosphorylation of at least one isoform of the Kv channel (Kv 1.2). These results demonstrate that S1P can activate the transcription factor CREB through different Ca2+-dependent pathways including intracellular Ca2+ release and inhibition of voltage-gated K+ channels leading to Ca2+ influx. Our findings suggest a potential role for S1P in regulation of gene expression in vascular smooth muscle. (C) 2003 Elsevier Inc. All rights reserved.

AB - Sphingosine 1-phosphate (SIP) is a potential mitogenic stimulus for vascular smooth muscle. S1P promotes an increase in the intracellular calcium concentration ([Ca2+](i)) in cerebral arteries, however S1P effects on regulation of gene expression are not known. Activation of the Ca2+-dependent transcription factor, cAMP response element-binding protein (CREB), is associated with smooth muscle proliferation. The aim of this study was to examine the Ca2+-dependent mechanisms involved in S1P-induced CREB activation in cerebral artery. Western blotting and immunofluorescence with a phospho-CREB antibody were used to detect CREB activation in Sprague-Dawley rat cerebral arteries. Whole-cell patch clamp recording and single cell imaging of [Ca2+]i were performed on freshly isolated cerebral artery myocytes. SIP increased activation of CREB in the nucleus of cerebral arteries. This activation was mediated by Ca2+/calmodulin-dependent protein kinase and was dependent on an increase in [Ca2+]i via two mechanisms: (i) intracellular Ca2+ release via an inositol 1,4,5-trisphosphate (InsP(3))-dependent pathway and (ii) Ca2+ entry through voltage-dependent Ca2+ channels (VDCC). Activation of the VDCC occurred through SIP-induced inhibition (approximately 50%) of the voltage-gated potassium (K+) current. This inhibition was via a protein kinase C-mediated pathway resulting in tyrosine phosphorylation of at least one isoform of the Kv channel (Kv 1.2). These results demonstrate that S1P can activate the transcription factor CREB through different Ca2+-dependent pathways including intracellular Ca2+ release and inhibition of voltage-gated K+ channels leading to Ca2+ influx. Our findings suggest a potential role for S1P in regulation of gene expression in vascular smooth muscle. (C) 2003 Elsevier Inc. All rights reserved.

KW - vascular smooth muscle

KW - transcription factor

KW - sphingosine 1-phosphate

KW - calcium release

KW - potassium channels

KW - calcium channels

KW - VASCULAR SMOOTH-MUSCLE

KW - ELEMENT-BINDING PROTEIN

KW - COUPLED RECEPTOR

KW - GENE-EXPRESSION

KW - INOSITOL 1,4,5-TRISPHOSPHATE

KW - MEMBRANE DEPOLARIZATION

KW - RYANODINE RECEPTORS

KW - CELL-PROLIFERATION

KW - MOLECULAR-CLONING

KW - NUCLEAR-FACTOR

U2 - 10.1016/S0006-2952(03)00546-X

DO - 10.1016/S0006-2952(03)00546-X

M3 - Article

VL - 66

SP - 1861

EP - 1870

JO - Biochemical Pharmacology

JF - Biochemical Pharmacology

SN - 0006-2952

IS - 9

ER -