Abstract |
Purine nucleosides protect neurons against hypoxic insult, but the signaling mechanisms have not yet been fully elucidated. We studied the role of the p42/44 MAPK pathway in purine nucleoside-mediated protection of cultured PC12 cells and primary cerebellar granule neurons from hypoxia-induced cell death. Incubation with adenosine reduced hypoxia-evoked cell death morphology, and increased the activity of the MAPK pathway. Inosine, a metabolic derivative of adenosine was generally less potent in PC12 cells. Pharmacological inhibition of the MAPK pathways severely hampered adenosine-mediated induction of cell viability and neurite outgrowth. Consistently, siRNA-mediated knockdown of p42 and p44 MAPK completely blocked adenosine-mediated rescue of hypoxic PC12 cells. The role of MAPK activation was further studied in primary neurons. Cells were significantly rescued by adenosine and inosine and siRNA-mediated knockdown severely affected purine-mediated rescue of neuronal viability after hypoxic insult. Results point to the important role of p42/44 MAPK for adenosine receptor-mediated neuroprotection.
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Authors | Bettina Tomaselli, Stephanie Zur Nedden, Valerie Podhraski, Gabriele Baier-Bitterlich |
Journal | Molecular and cellular neurosciences
(Mol Cell Neurosci)
Vol. 38
Issue 4
Pg. 559-68
(Aug 2008)
ISSN: 1095-9327 [Electronic] United States |
PMID | 18585057
(Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Neuroprotective Agents
- Purine Nucleosides
- Mitogen-Activated Protein Kinase 1
- Mitogen-Activated Protein Kinase 3
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Topics |
- Animals
- Cell Hypoxia
(drug effects, physiology)
- Cell Survival
(drug effects, physiology)
- Cells, Cultured
- Cerebellum
(drug effects, enzymology, pathology)
- Cytoplasmic Granules
(drug effects, enzymology, pathology)
- Mitogen-Activated Protein Kinase 1
(antagonists & inhibitors, physiology)
- Mitogen-Activated Protein Kinase 3
(antagonists & inhibitors, physiology)
- Neurons
(drug effects, enzymology, pathology)
- Neuroprotective Agents
(pharmacology)
- PC12 Cells
- Purine Nucleosides
(pharmacology)
- Rats
- Rats, Sprague-Dawley
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