Stimulation of the Cyclic GMP Pathway by NO Induces Expression of the Immediate Early Genes c-fos and junB in PC12 Cells
Article first published online: 23 NOV 2002
Journal of Neurochemistry
Volume 62, Issue 2, pages 496–501, February 1994
How to Cite
Haby, C., Lisovoski, F., Aunis, D. and Zwiller, J. (1994), Stimulation of the Cyclic GMP Pathway by NO Induces Expression of the Immediate Early Genes c-fos and junB in PC12 Cells. Journal of Neurochemistry, 62: 496–501. doi: 10.1046/j.1471-4159.1994.62020496.x
- Issue published online: 23 NOV 2002
- Article first published online: 23 NOV 2002
- Received April 20, 1993; revised manuscript received June 28, 1993; accepted June 28, 1993.
- Cyclic GMP;
- Early genes;
- Guanylate cyclase;
- Cyclic GMP-dependent protein kinase
Abstract: Stimulation of several second messenger pathways induces the expression of immediate early genes such as c-fos, c-jun, junB, and junD, but little is known about their induction via the stimulation of the cyclic GMP pathway. Here we looked at the expression of early genes in pheochromocytoma PC12 cells after activation of cytosolic guanylate cyclase by sodium nitroprusside. This compound spontaneously releases NO, a molecule known to be involved in cell communication. We found that expression of c-fos and junB but not of c-jun or junD is increased upon activation of cyclic GMP pathway. c-fos mRNA expression was the most activated (fourfold at 30 min), whereas junB response was more modest (2.2-fold activation at 60 min). Nuclear extracts of stimulated cells show increased binding capacity to the AP1 binding site consistent with the dose-response curve. The activating effect of nitroprusside could be reproduced by dipyridamole, a selective cyclic GMP phosphodiesterase inhibitor and by 8-p-chlorophenylthio-cyclic GMP, a permeant selective cyclic GMP-dependent protein kinase activator, and abolished by KT5823, an inhibitor of that kinase. The results show that NO promotes early gene activation and AP1 binding enhancement through the stimulation of the cyclic GMP pathway.