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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
Author(s) -
Ciani Elisabetta,
Guidi Sandra,
Bartesaghi Renata,
Contestabile Antonio
Publication year - 2002
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.2002.01080.x
Subject(s) - creb , microbiology and biotechnology , nitric oxide , biology , phosphorylation , protein kinase b , protein kinase a , kinase , nitric oxide synthase , signal transduction , transcription factor , chemistry , biochemistry , endocrinology , gene
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.