Glucocorticoids modulate G-protein α-subunit levels in PC 12 cells

Xiaohua Li, Richard S. Jope

Research output: Contribution to journalArticle

7 Scopus citations

Abstract

Regulation by the synthetic glucocorticoid hormone, dexamethasone, of the levels of several G-protein a-subunits was studied during differentiation in PC12 cells. Similar patterns, although with different magnitudes, were observed in the changes in the levels of αil, αs, and αq induced by the treatments studied, whereas αo differed from the other α-subunits. Thus, nerve growth factor (NGF) treatment increased αil, αs, and αq, and forskolin increased αil and αq, with the increase in αil being greater than the increases in the other two α-subunits after both treatments. The increases in αil, αs, and αq 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 αil, αs, and αq induced by NGF or forskolin, almost completely blocking any changes from control levels. The level of αo also was increased in PC12 cells by treatment with NGF or forskolin, but, in contrast to the other G-protein α-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 αo subtypes, αol and αo2, so they were expressed in a ratio of 1:2 in PC 12 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 α-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.

Original languageEnglish (US)
Pages (from-to)213-220
Number of pages8
JournalBrain Research
Volume759
Issue number2
DOIs
StatePublished - Jun 6 1997
Externally publishedYes

Keywords

  • Dexamethasone
  • G-protein
  • Glucocorticoid
  • Nerve growth factor
  • Signal transduction

ASJC Scopus subject areas

  • Neuroscience(all)

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