Mechanism of isoproterenol-induced RGS2 up-regulation in astrocytes

作者：Kim Sung Dae; Lee Whi Min; Suk Kyoungho; Park Seung Chun; Kim Sang Keun; Cho Jae Youl; Rhee Man Hee^*

来源：Biochemical and Biophysical Research Communications, 2006, 349(1): 408-415.

DOI：10.1016/j.bbrc.2006.08.061

• RGS2
• astrocytes
• isoproterenol
• adrenergic receptor
• protein kinase C
• p38 mitogen-activated protein kinase

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). alpha-Adrenergic antagonist (prazocin), beta-adrenergic antagonist (prazocin), and pertussis toxin only partially blocked the RGS2 up-regulation, suggesting that the RGS2 up-regulation is concomitantly mediated by G alpha(i), G alpha(s), and G alpha(q). 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.

• 出版日期2006-10-13