Norepinephrine and nitric oxide promote cell survival signaling in hippocampal neurons
| Autor: | Amelia A. Russo-Neustadt, Michael J. Chen, Neha J. Patel |
|---|---|
| Rok vydání: | 2010 |
| Předmět: |
Nitroprusside
medicine.medical_specialty Cell Survival Biology Nitric Oxide Hippocampus Neuroprotection Clonidine Nitric oxide Rats Sprague-Dawley Norepinephrine chemistry.chemical_compound Pregnancy Stress Physiological Neurotrophic factors Internal medicine medicine Animals Cyclic AMP Response Element-Binding Protein Extracellular Signal-Regulated MAP Kinases Neurotransmitter Cells Cultured Neurons Pharmacology Brain-derived neurotrophic factor Brain-Derived Neurotrophic Factor Rats Nitric oxide synthase NG-Nitroarginine Methyl Ester Neuroprotective Agents Endocrinology chemistry Food Catecholamine biology.protein Female Proto-Oncogene Proteins c-akt Signal Transduction medicine.drug |
| Zdroj: | European Journal of Pharmacology. 633:1-9 |
| ISSN: | 0014-2999 |
| DOI: | 10.1016/j.ejphar.2010.01.012 |
| Popis: | Nitric oxide (NO), physical exercise and/or antidepressant drugs, through the increased release of norepinephrine and brain-derived neurotrophic factor (BDNF), have been shown to exert profound protective, pro-survival effects on neurons otherwise compromised by injury, disease, prolonged stress, and subsequent depression in vivo. We sought, therefore, to evaluate such survival and neuroprotection in hippocampal neurons in culture, which, in an analogous model of in vivo cellular stress, was deprived of several vital nutrients. We assessed pro-survival outcomes following the application of norepinephrine or the noradrenergic partial agonist, clonidine, a general nitric oxide synthase inhibitor and NO donor, using a cell survival assay and quantitative Western blotting of the survival signaling molecules, BDNF, P-CREB, P-Akt, and P-MAPK in hippocampal neuronal lysates. We demonstrate that norepinephrine, clonidine, the NO donor and various combinations of these drugs increased cell survival and the immunoreactivity of the four survival signaling molecules in the face of nutrient deprivation stress, whereas the NO synthase inhibitor, and each of several survival signaling pathway inhibitors all decreased cell survival even below that of controls without nutrient supplementation. These results demonstrate that conditions that make cells vulnerable to environmental/toxic insult can be offset by norepinephrine and its related drugs or by NO donors and exacerbated by drugs that specifically inhibit a key survival signaling pathway. These results indicate that pharmacological intervention can promote neuroprotection and survival signaling in the face of nutrient withdrawal, but that this may require that several pathways remain intact. |
| Databáze: | OpenAIRE |
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