title: p42/44 MAPK is an essential effector for purine nucleoside-mediated neuroprotection of hypoxic PC12 cells and primary cerebellar granule neurons.
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.
authors.affiliation: Biocenter, Division of Neurobiochemistry, Medical University of Innsbruck, Fritz Pregl Str.3, A-6020 Innsbruck, Austria.
authors.forename: Bettina
authors.initials: B
authors.lastname: Tomaselli
authors.forename: Stephanie Zur
authors.initials: SZ
authors.lastname: Nedden
authors.forename: Valerie
authors.initials: V
authors.lastname: Podhraski
authors.forename: Gabriele
authors.initials: G
authors.lastname: Baier-Bitterlich
mesh_terms: D000818:Animals; D015687:Cell Hypoxia / Q000187:drug effects / Q000502:physiology; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D002531:Cerebellum / Q000187:drug effects / Q000201:enzymology* / Q000473:pathology; D003594:Cytoplasmic Granules / Q000187:drug effects / Q000201:enzymology* / Q000473:pathology; D019950:Mitogen-Activated Protein Kinase 1 / Q000037:antagonists & inhibitors / Q000502:physiology*; D048052:Mitogen-Activated Protein Kinase 3 / Q000037:antagonists & inhibitors / Q000502:physiology*; D009474:Neurons / Q000187:drug effects / Q000201:enzymology* / Q000473:pathology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D016716:PC12 Cells; D011684:Purine Nucleosides / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D018696:Neuroprotective Agents; D011684:Purine Nucleosides; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3