TY - JOUR
T1 - Characterization of thromboxane A2 receptor signaling in developing rat oligodendrocytes
T2 - Nuclear receptor localization and stimulation of myelin basic protein expression
AU - Ramamurthy, Santosh
AU - Mir, Fozia
AU - Gould, Robert M.
AU - Le Breton, Guy C.
PY - 2006/11/15
Y1 - 2006/11/15
N2 - The present work investigates the role of thromboxane A2 (TXA2) receptors in the development of oligodendrocytes (OLGs), The results demonstrate that the proteins of the TXA2 signaling pathway, i.e., cyclooxygenase (COX-1), TXA2 synthase (TS), and TXA2 receptor (TPR) are expressed in the developing rat brain during myelination. Furthermore, culture of OLG progenitor cells (OPCs) revealed that the expression levels of these proteins as well as TXA2 synthesis increase during OLG maturation. Separate studies established that activation of TPRs by the agonist U46619 increases intracellular calcium in both OPCs and OLGs as visualized by digital fluorescence imaging. Immunocytochemical staining demonstrated that TPRs are localized in the plasma membrane and perinuclear compartments in OPCs. However, during OLG differentiation, TPRs shift their localization pattern and also become associated with the nuclear compartment. This shift to nuclear localization was confirmed by biochemical analysis in cultured cells and by immunocytochemical analysis in developing rat brain. Finally, it was found that U46619 activation of TPRs in maturing OLGs resulted in enhanced myelin basic protein (MBP) expression. Alternatively, inhibition of endogenous TPR signaling led to reduced MBP expression. Furthermore, TPR-mediated MBP expression was found to be associated with increased transcription from the MBP promoter using a MBP-luciferase reporter. Collectively, these findings suggest a novel TPR signaling pathway in OLGs and a potential role for this signaling during OLG maturation and myelin production.
AB - The present work investigates the role of thromboxane A2 (TXA2) receptors in the development of oligodendrocytes (OLGs), The results demonstrate that the proteins of the TXA2 signaling pathway, i.e., cyclooxygenase (COX-1), TXA2 synthase (TS), and TXA2 receptor (TPR) are expressed in the developing rat brain during myelination. Furthermore, culture of OLG progenitor cells (OPCs) revealed that the expression levels of these proteins as well as TXA2 synthesis increase during OLG maturation. Separate studies established that activation of TPRs by the agonist U46619 increases intracellular calcium in both OPCs and OLGs as visualized by digital fluorescence imaging. Immunocytochemical staining demonstrated that TPRs are localized in the plasma membrane and perinuclear compartments in OPCs. However, during OLG differentiation, TPRs shift their localization pattern and also become associated with the nuclear compartment. This shift to nuclear localization was confirmed by biochemical analysis in cultured cells and by immunocytochemical analysis in developing rat brain. Finally, it was found that U46619 activation of TPRs in maturing OLGs resulted in enhanced myelin basic protein (MBP) expression. Alternatively, inhibition of endogenous TPR signaling led to reduced MBP expression. Furthermore, TPR-mediated MBP expression was found to be associated with increased transcription from the MBP promoter using a MBP-luciferase reporter. Collectively, these findings suggest a novel TPR signaling pathway in OLGs and a potential role for this signaling during OLG maturation and myelin production.
KW - Cyclooxygenase-1
KW - Myelin basic protein
KW - Oligodendrocyte
KW - Thromboxane A receptor
KW - Thromboxane A synthase
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U2 - 10.1002/jnr.21061
DO - 10.1002/jnr.21061
M3 - Article
C2 - 16998891
AN - SCOPUS:33750600719
VL - 84
SP - 1402
EP - 1414
JO - Journal of Neuroscience Research
JF - Journal of Neuroscience Research
SN - 0360-4012
IS - 7
ER -