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 language | English |
|---|---|
| Pages (from-to) | 213-220 |
| Number of pages | 8 |
| Journal | Brain Research |
| Volume | 759 |
| Issue number | 2 |
| DOIs | |
| State | Published - Jun 6 1997 |
| Externally published | Yes |
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Keywords
- Dexamethasone
- G-protein
- Glucocorticoid
- Nerve growth factor
- Signal transduction
ASJC Scopus subject areas
- Neuroscience(all)
Cite this
Glucocorticoids modulate G-protein α-subunit levels in PC 12 cells. / Li, Xiaohua; Jope, Richard S.
In: Brain Research, Vol. 759, No. 2, 06.06.1997, p. 213-220.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Glucocorticoids modulate G-protein α-subunit levels in PC 12 cells
AU - Li, Xiaohua
AU - Jope, Richard S
PY - 1997/6/6
Y1 - 1997/6/6
N2 - 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.
AB - 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.
KW - Dexamethasone
KW - G-protein
KW - Glucocorticoid
KW - Nerve growth factor
KW - Signal transduction
UR - http://www.scopus.com/inward/record.url?scp=0030807583&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0030807583&partnerID=8YFLogxK
U2 - 10.1016/S0006-8993(97)00256-4
DO - 10.1016/S0006-8993(97)00256-4
M3 - Article
C2 - 9221939
AN - SCOPUS:0030807583
VL - 759
SP - 213
EP - 220
JO - Brain Research
JF - Brain Research
SN - 0006-8993
IS - 2
ER -