TY - JOUR
T1 - Mechanism of isoproterenol-induced RGS2 up-regulation in astrocytes
AU - Kim, Sung Dae
AU - Lee, Whi Min
AU - Suk, Kyoungho
AU - Park, Seung Chun
AU - Kim, Sang Keun
AU - Cho, Jae Youl
AU - Rhee, Man Hee
PY - 2006/10/13
Y1 - 2006/10/13
N2 - Regulators of G protein signaling (RGSs) are inducibly expressed in response to various stimuli and the up-regulation of RGSs leads to significant decreases in GPCR responsiveness. Isoproterenol, an adrenergic receptor agonist, stimulated RGS2 mRNA in C6 rat astrocytoma cells. The up-regulation of RGS2 mRNA was abrogated by genistein, a protein tyrosine kinase inhibitor (PTK), and by broad-spectrum protein kinase C (PKC) inhibitors (staurosporine and GF109203X). α-Adrenergic antagonist (prazocin), β-adrenergic antagonist (prazocin), and pertussis toxin only partially blocked the RGS2 up-regulation, suggesting that the RGS2 up-regulation is concomitantly mediated by Gαi, Gαs, and Gαq. It is interesting to note that SB203580, a potent p38 mitogen-activated protein kinase (MAPK) inhibitor, completely inhibited the isoproterenol-mediated RGS2 expression. In addition, isoproterenol also markedly stimulated RGS2 mRNA in rat primary astrocytes, which were sensitive to SB203580 and staurosporine. Therefore, our data suggest that adrenergic receptor-mediated signaling (induced by isoproterenol) may be involved in the regulation of RGS2 expression in astrocytes via activating PTK, PKC, and p38 MAPK.
AB - Regulators of G protein signaling (RGSs) are inducibly expressed in response to various stimuli and the up-regulation of RGSs leads to significant decreases in GPCR responsiveness. Isoproterenol, an adrenergic receptor agonist, stimulated RGS2 mRNA in C6 rat astrocytoma cells. The up-regulation of RGS2 mRNA was abrogated by genistein, a protein tyrosine kinase inhibitor (PTK), and by broad-spectrum protein kinase C (PKC) inhibitors (staurosporine and GF109203X). α-Adrenergic antagonist (prazocin), β-adrenergic antagonist (prazocin), and pertussis toxin only partially blocked the RGS2 up-regulation, suggesting that the RGS2 up-regulation is concomitantly mediated by Gαi, Gαs, and Gαq. It is interesting to note that SB203580, a potent p38 mitogen-activated protein kinase (MAPK) inhibitor, completely inhibited the isoproterenol-mediated RGS2 expression. In addition, isoproterenol also markedly stimulated RGS2 mRNA in rat primary astrocytes, which were sensitive to SB203580 and staurosporine. Therefore, our data suggest that adrenergic receptor-mediated signaling (induced by isoproterenol) may be involved in the regulation of RGS2 expression in astrocytes via activating PTK, PKC, and p38 MAPK.
KW - Adrenergic receptor
KW - Astrocytes
KW - Isoproterenol
KW - P38 mitogen-activated protein kinase
KW - Protein kinase C
KW - RGS2
UR - http://www.scopus.com/inward/record.url?scp=33748312082&partnerID=8YFLogxK
U2 - 10.1016/j.bbrc.2006.08.061
DO - 10.1016/j.bbrc.2006.08.061
M3 - Article
C2 - 16934753
AN - SCOPUS:33748312082
SN - 0006-291X
VL - 349
SP - 408
EP - 415
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
IS - 1
ER -