Nitric oxide regulates cGMP-dependent cAMP-responsive element binding protein phosphorylation and Bcl-2 expression in cerebellar neurons: implication for a survival role of nitric oxide
Article first published online: 3 FEB 2004
Journal of Neurochemistry
Volume 82, Issue 5, pages 1282–1289, September 2002
How to Cite
Ciani, E., Guidi, S., Bartesaghi, R. and Contestabile, A. (2002), Nitric oxide regulates cGMP-dependent cAMP-responsive element binding protein phosphorylation and Bcl-2 expression in cerebellar neurons: implication for a survival role of nitric oxide. Journal of Neurochemistry, 82: 1282–1289. doi: 10.1046/j.1471-4159.2002.01080.x
- Issue published online: 3 FEB 2004
- Article first published online: 3 FEB 2004
- Received January 29, 2002; revised manuscript received May 6, 2002; accepted May 30, 2002.
- cerebellar granule cells;
- guanylate cyclase;
- nitric oxide;
Nitric oxide (NO) is a small, diffusible, highly reactive molecule with a dichotomous regulatory role in the brain: an intra- and intercellular messenger under physiological conditions and a neurodegenerative agent under pathological conditions. We have recently demonstrated that long-lasting exposure to an neuronal nitric oxide synthase (nNOS) inhibitor down-regulated serine/threonine kinase (Akt) survival pathway and caused apoptosis in cerebellar granule cell cultures. The present study further substantiates the role of NO in neuronal survival by demonstrating that blocking its production down-regulates the activity of cAMP-responsive element binding protein (CREB), a transcription factor involved in cell survival and synaptic plasticity. Pharmacological dissection of the pathway linking NO to CREB shows that cGMP and its kinase are intermediate effectors. We also identify Bcl-2 as one of the anti-apoptotic genes down-regulated by NO shortage and decreased CREB phosphorylation. These results not only confirm the role of CREB in neuronal survival but also provide circumstantial evidence for a novel link among NO, CREB activation and survival.