Glucocorticoids modulate G-protein alpha-subunit levels in PC12 cells.
Regulation by the synthetic glucocorticoid hormone, dexamethasone, of the levels of several G-protein alpha-subunits was studied during differentiation in PC12 cells. Similar patterns, although with different magnitudes, were observed in the changes in the levels of alpha il, alpha s, and alpha q induced by the treatments studied, whereas alpha o differed from the other alpha-subunits. Thus, nerve growth factor (NGF) treatment increased alpha il, alpha s, and alpha q, and forskolin increased alpha il and alpha q, with the increase in alpha il being greater than the increases in the other two alpha-subunits after both treatments. The increases in alpha il, alpha s, and alpha q induced by NGF were dependent on signaling through ras, since they did not occur in NGF-treated M17 cells, which express a dominant inhibitory Ha-ras. Treatment of PC12 cells with dexamethasone antagonized the increases in alpha il, alpha s, and alpha q induced by NGF or forskolin, almost completely blocking any changes from control levels. The level of alpha o also was increased in PC12 cells by treatment with NGF or forskolin, but, in contrast to the other G-protein alpha-subunits, the response to NGF was not antagonized by dexamethasone in PC12 cells, or by the deficient ras activity in M17 cells. However, ras influenced the alternative splicing that regulates the levels of the two alpha o subtypes, beta o1 and alpha o2, so they were expressed in a ratio of 1:2 in PC12 cells but 2:1 in ras-deficient M17 cells. These results demonstrated marked, and subtype-selective, influences of dexamethasone on the levels of G-protein alpha-subunits, an effect that may contribute to the effects of conditions that increase the levels of glucocorticoid hormones, such as stress or certain diseases, on signal transduction processes in brain.
Li
X
X
Department of Psychiatry and Behavioral Neurobiology, University of Alabama at Birmingham, 35294-0017, USA.
Jope
R S
RS
D000818:Animals; D003907:Dexamethasone / Q000494:pharmacology; D019204:GTP-Binding Proteins / Q000187:drug effects*; D005938:Glucocorticoids / Q000494:pharmacology*; D009414:Nerve Growth Factors / Q000494:pharmacology; D016716:PC12 Cells / Q000187:drug effects*; D051381:Rats
D005938:Glucocorticoids; D009414:Nerve Growth Factors; D003907:Dexamethasone; D019204:GTP-Binding Proteins