Journal of neurochemistry, 2010-04, Vol.113 (2), p.432-446
2010
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Details
- Autor(en) / Beteiligte
- Titel
- Vital role of protein kinase C-related kinase in the formation and stability of neurites during hypoxia
- Ist Teil von
- Journal of neurochemistry, 2010-04, Vol.113 (2), p.432-446
- Ort / Verlag
- Oxford, UK: Oxford, UK : Blackwell Publishing Ltd
- Erscheinungsjahr
- 2010
- Quelle
- Wiley-Blackwell Journals
- Beschreibungen/Notizen
- J. Neurochem. (2010) 113, 432-446. Exposure of pheochromocytoma cells to hypoxia (1% O₂) favors differentiation at the expense of cell viability. Additional incubation with nerve growth factor (NGF) and guanosine, a purine nucleoside with neurotrophin characteristics, rescued cell viability and further enhanced the extension of neurites. In parallel, an increase in the activity of protein kinase C-related kinase (PRK1), which is known to be involved in regulation of the actin cytoskeleton, was observed in hypoxic cells. NGF and guanosine further enhanced PRK1 in normoxic and hypoxic cells. To study the role of PRK1 during cellular stress response and neurotrophin-mediated signaling, pheochromocytoma cells were transfected with small interfering RNA directed against PRK1. Loss of functional PRK1 initiated a significant loss of viability and inhibited neurite formation. SiRNA-mediated knockdown of PRK1 also completely stalled guanosine-mediated neuroprotective effects. Additionally, the F-actin-associated cytoskeleton and the expression of the plasticity protein growth associated protein-43 were disturbed upon PRK1 knockdown. A comparable dependency of neurite formation and growth associated protein-43 immunoreactivity on functional PRK1 expression was observed in cerebellar granule neurons. Based on these data, a putative role of PRK1 as a key-signaling element for the successive NGF- and purine nucleoside-mediated protection of hypoxic neuronal cells is hypothesized.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 0022-3042eISSN: 1471-4159DOI: 10.1111/j.1471-4159.2010.06624.xTitel-ID: cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_2967713
- Format
- –
- Schlagworte
- Adrenals. Adrenal axis. Renin-angiotensin system (diseases), Animals, Animals, Newborn, Biological and medical sciences, Cell Death - drug effects, Cell Hypoxia - physiology, Cell Survival - drug effects, Cell Survival - physiology, Cells, Cultured, cerebellar granule neurons, Cerebellum - cytology, Drug Interactions, Endocrinopathies, Fundamental and applied biological sciences. Psychology, GAP-43 Protein - metabolism, guanosine, Guanosine - pharmacology, Hypoxia, Isolated neuron and nerve. Neuroglia, Medical sciences, Nerve Growth Factor - pharmacology, Neurites - drug effects, Neurites - physiology, Neurons - cytology, Neurons - drug effects, neuroprotection, Non tumoral diseases. Target tissue resistance. Benign neoplasms, Oncogene Protein v-akt - metabolism, pheochromocytoma cells, Protein Kinase C - genetics, Protein Kinase C - metabolism, protein kinase C-related kinase 1, Proteins, Rats, Rats, Sprague-Dawley, RNA, Small Interfering - pharmacology, Stress analysis, Transfection - methods, Vertebrates: nervous system and sense organs