Interferon gamma induces protective non-canonical signaling pathways in primary neurons
| Autor: | Lauren A. O’Donnell, Anil K. Pattisapu, Siddharth Balachandran, Glenn F. Rall, Kristen M. Henkins, Christine M. Matullo, Apurva Kulkarni |
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| Rok vydání: | 2014 |
| Předmět: |
MAPK/ERK pathway
Antimetabolites Cell Survival MAP Kinase Signaling System Primary Cell Culture Mice Transgenic Biology Hippocampal formation Biochemistry Hippocampus Article Cellular and Molecular Neuroscience Interferon-gamma Mice Cytosol Interferon Pregnancy medicine Animals Interferon gamma STAT1 Protein Kinase Inhibitors Neurons Staurosporine Cell biology medicine.anatomical_structure Neuroprotective Agents Bromodeoxyuridine Apoptosis biology.protein Female Neuron Signal transduction Neuroglia medicine.drug Signal Transduction |
| Zdroj: | Journal of Neurochemistry |
| ISSN: | 1471-4159 |
| Popis: | The signal transduction molecule, Stat1, is critical for the expression of type I and II interferon (IFN)-responsive genes in most cells; however, we previously showed that primary hippocampal mouse neurons express low basal Stat1, with delayed and attenuated expression of IFN-responsive genes. Moreover, IFNγ-dependent resolution of a neurotropic viral challenge in permissive mice is Stat1-independent. Here, we show that exogenous IFNγ has no deleterious impact on neuronal viability, and staurosporine-induced apoptosis in neurons is significantly blunted by the addition of IFNγ, suggesting that IFNγ confers a pro-survival signal in neurons. To identify the pathways induced by IFNγ in neurons, the activation of alternative signal transducers associated with IFNγ signaling was assessed. Rapid and pronounced activation of extracellular signal regulated kinase (Erk1/2) was observed in neurons, compared to a modest response in fibroblasts. Moreover, the absence of Stat1 in primary fibroblasts led to enhanced Erk activation following IFNγ addition, implying that the cell-specific availability of signal transducers can diversify the cellular response following IFN engagement. |
| Databáze: | OpenAIRE |
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