Amplification of calcium-induced gene transcription by nitric oxide in neuronal cells

Nitric oxide (NO) is a short-lived, highly reactive gas, which has been identified as a mediator in vasodilation, an active agent in macrophage cytotoxicity and neurotoxicity, and a neuro-transmitter in the central and peripheral nervous systems. Production of NO by neurons is critical for facilitat...

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Bibliographic Details
Published in:Nature (London) 1993-07, Vol.364 (6436), p.450-453
Main Authors: Peunova, Natalia, Enikolopov, Grigori
Format: Article
Language:English
Subjects:
Animals
Base Sequence
Biochemistry
Calcium
Calcium - physiology
Cyclic GMP - metabolism
Cytotoxicity
Drug Synergism
Gases
Genes, fos - drug effects
Genes, jun - drug effects
Molecular Sequence Data
Neurons
Neurons - drug effects
Neurons - metabolism
Neurotoxicity
Nitric oxide
Nitric Oxide - pharmacology
PC12 Cells
Protein Kinases - physiology
Regulatory Sequences, Nucleic Acid - physiology
Transcription, Genetic - drug effects
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Summary:Nitric oxide (NO) is a short-lived, highly reactive gas, which has been identified as a mediator in vasodilation, an active agent in macrophage cytotoxicity and neurotoxicity, and a neuro-transmitter in the central and peripheral nervous systems. Production of NO by neurons is critical for facilitated synaptic transmission in models of synaptic plasticity such as long-term potentiation and long-term depression, suggesting a role for NO as a retrograde messenger that could complete a hypothetical feedback loop by strengthening the connection between postsynaptic and presynaptic cells. We report here that although alone NO has no evident effect on transcription, it can act as an amplifier of calcium signals in neuronal cells. NO and Ca2+ action have to coincide in time for amplification to occur. Experiments with a series of simplified reporter genes in combination with specific recombinant protein kinase inhibitors suggest that induction of gene activity following NO-amplified calcium action involves protein kinase A-dependent activation of the transcription factor CREB.
ISSN:0028-0836
1476-4687
DOI:10.1038/364450a0