Thromboxane A2 receptor-mediated cell proliferation, survival and gene expression in oligodendrocytes

Xin Lin, Santosh K. Ramamurthy, Guy C. Le Breton

Research output: Contribution to journalArticle

Abstract

Thromboxane A2 receptors (TP) were previously localized to discrete regions in the rat brain on myelinated fiber tracts and oligodendrocytes (OLGs). The present studies extended these findings and investigated the effects of TP signaling on cell proliferation, survival, and gene expression in OLG progenitor cells (OPCs) and OLGs. It was found that the TP agonist, U46619 stimulated the proliferation of OPCs and promoted the survival of mature OLGs. Examination of the early gene expression events involved in OPC proliferation, revealed that c-fos expression was substantially increased by U46619 stimulation. Treatment of OPCs or OLGs with U46619 caused activation of the mitogen-activated protein kinases (MAPK) ERK 1/2. In OPCs this activation was blocked by inhibition of src. However, in OLGs this phosphorylation was not only blocked by inhibition of src but also by inhibition of protein kinase C (PKC). Furthermore, U46619 was found to increase CREB phosphorylation in both OPCs and OLGs. Similar to ERK 1/2 activation, there was a divergence in the mechanism of the TP-mediated CREB response for each cell type. Specifically, U46619 activation was attenuated by src and protein kinase A (PKA) inhibition in OPCs, whereas in OLGs this effect was blocked by inhibition of src, PKA as well as by inhibition of PKC. Collectively, these results provide the first demonstration that TP-activated nuclear signaling events are involved in the proliferation of OPCs, the survival of mature OLGs, and the stimulation of gene expression.

Original languageEnglish (US)
Pages (from-to)257-268
Number of pages12
JournalJournal of Neurochemistry
Volume93
Issue number2
DOIs
StatePublished - Apr 2005
Externally publishedYes

Fingerprint

Prostaglandin H2 Receptors Thromboxane A2
15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid
Oligodendroglia
Cell proliferation
Gene expression
Cell Survival
Cell Proliferation
Stem Cells
Gene Expression
Chemical activation
Phosphorylation
Cyclic AMP-Dependent Protein Kinases
Protein Kinase C
src-Family Kinases
Mitogen-Activated Protein Kinases
Rats
Brain
Demonstrations
Fibers

Keywords

  • CREB
  • ERK1/2
  • Oligodendrocyte
  • Proliferation
  • Survival
  • Thromboxane A receptor

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

Cite this

Thromboxane A2 receptor-mediated cell proliferation, survival and gene expression in oligodendrocytes. / Lin, Xin; Ramamurthy, Santosh K.; Le Breton, Guy C.

In: Journal of Neurochemistry, Vol. 93, No. 2, 04.2005, p. 257-268.

Research output: Contribution to journalArticle

Lin, Xin ; Ramamurthy, Santosh K. ; Le Breton, Guy C. / Thromboxane A2 receptor-mediated cell proliferation, survival and gene expression in oligodendrocytes. In: Journal of Neurochemistry. 2005 ; Vol. 93, No. 2. pp. 257-268.
@article{253404fed549440abb00b4b52d53ef8b,
title = "Thromboxane A2 receptor-mediated cell proliferation, survival and gene expression in oligodendrocytes",
abstract = "Thromboxane A2 receptors (TP) were previously localized to discrete regions in the rat brain on myelinated fiber tracts and oligodendrocytes (OLGs). The present studies extended these findings and investigated the effects of TP signaling on cell proliferation, survival, and gene expression in OLG progenitor cells (OPCs) and OLGs. It was found that the TP agonist, U46619 stimulated the proliferation of OPCs and promoted the survival of mature OLGs. Examination of the early gene expression events involved in OPC proliferation, revealed that c-fos expression was substantially increased by U46619 stimulation. Treatment of OPCs or OLGs with U46619 caused activation of the mitogen-activated protein kinases (MAPK) ERK 1/2. In OPCs this activation was blocked by inhibition of src. However, in OLGs this phosphorylation was not only blocked by inhibition of src but also by inhibition of protein kinase C (PKC). Furthermore, U46619 was found to increase CREB phosphorylation in both OPCs and OLGs. Similar to ERK 1/2 activation, there was a divergence in the mechanism of the TP-mediated CREB response for each cell type. Specifically, U46619 activation was attenuated by src and protein kinase A (PKA) inhibition in OPCs, whereas in OLGs this effect was blocked by inhibition of src, PKA as well as by inhibition of PKC. Collectively, these results provide the first demonstration that TP-activated nuclear signaling events are involved in the proliferation of OPCs, the survival of mature OLGs, and the stimulation of gene expression.",
keywords = "CREB, ERK1/2, Oligodendrocyte, Proliferation, Survival, Thromboxane A receptor",
author = "Xin Lin and Ramamurthy, {Santosh K.} and {Le Breton}, {Guy C.}",
year = "2005",
month = "4",
doi = "10.1111/j.1471-4159.2004.02969.x",
language = "English (US)",
volume = "93",
pages = "257--268",
journal = "Journal of Neurochemistry",
issn = "0022-3042",
publisher = "Wiley-Blackwell",
number = "2",

}

TY - JOUR

T1 - Thromboxane A2 receptor-mediated cell proliferation, survival and gene expression in oligodendrocytes

AU - Lin, Xin

AU - Ramamurthy, Santosh K.

AU - Le Breton, Guy C.

PY - 2005/4

Y1 - 2005/4

N2 - Thromboxane A2 receptors (TP) were previously localized to discrete regions in the rat brain on myelinated fiber tracts and oligodendrocytes (OLGs). The present studies extended these findings and investigated the effects of TP signaling on cell proliferation, survival, and gene expression in OLG progenitor cells (OPCs) and OLGs. It was found that the TP agonist, U46619 stimulated the proliferation of OPCs and promoted the survival of mature OLGs. Examination of the early gene expression events involved in OPC proliferation, revealed that c-fos expression was substantially increased by U46619 stimulation. Treatment of OPCs or OLGs with U46619 caused activation of the mitogen-activated protein kinases (MAPK) ERK 1/2. In OPCs this activation was blocked by inhibition of src. However, in OLGs this phosphorylation was not only blocked by inhibition of src but also by inhibition of protein kinase C (PKC). Furthermore, U46619 was found to increase CREB phosphorylation in both OPCs and OLGs. Similar to ERK 1/2 activation, there was a divergence in the mechanism of the TP-mediated CREB response for each cell type. Specifically, U46619 activation was attenuated by src and protein kinase A (PKA) inhibition in OPCs, whereas in OLGs this effect was blocked by inhibition of src, PKA as well as by inhibition of PKC. Collectively, these results provide the first demonstration that TP-activated nuclear signaling events are involved in the proliferation of OPCs, the survival of mature OLGs, and the stimulation of gene expression.

AB - Thromboxane A2 receptors (TP) were previously localized to discrete regions in the rat brain on myelinated fiber tracts and oligodendrocytes (OLGs). The present studies extended these findings and investigated the effects of TP signaling on cell proliferation, survival, and gene expression in OLG progenitor cells (OPCs) and OLGs. It was found that the TP agonist, U46619 stimulated the proliferation of OPCs and promoted the survival of mature OLGs. Examination of the early gene expression events involved in OPC proliferation, revealed that c-fos expression was substantially increased by U46619 stimulation. Treatment of OPCs or OLGs with U46619 caused activation of the mitogen-activated protein kinases (MAPK) ERK 1/2. In OPCs this activation was blocked by inhibition of src. However, in OLGs this phosphorylation was not only blocked by inhibition of src but also by inhibition of protein kinase C (PKC). Furthermore, U46619 was found to increase CREB phosphorylation in both OPCs and OLGs. Similar to ERK 1/2 activation, there was a divergence in the mechanism of the TP-mediated CREB response for each cell type. Specifically, U46619 activation was attenuated by src and protein kinase A (PKA) inhibition in OPCs, whereas in OLGs this effect was blocked by inhibition of src, PKA as well as by inhibition of PKC. Collectively, these results provide the first demonstration that TP-activated nuclear signaling events are involved in the proliferation of OPCs, the survival of mature OLGs, and the stimulation of gene expression.

KW - CREB

KW - ERK1/2

KW - Oligodendrocyte

KW - Proliferation

KW - Survival

KW - Thromboxane A receptor

UR - http://www.scopus.com/inward/record.url?scp=17444422791&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=17444422791&partnerID=8YFLogxK

U2 - 10.1111/j.1471-4159.2004.02969.x

DO - 10.1111/j.1471-4159.2004.02969.x

M3 - Article

C2 - 15816849

AN - SCOPUS:17444422791

VL - 93

SP - 257

EP - 268

JO - Journal of Neurochemistry

JF - Journal of Neurochemistry

SN - 0022-3042

IS - 2

ER -