期刊
JOURNAL OF NEUROCHEMISTRY
卷 113, 期 2, 页码 432-446出版社
WILEY
DOI: 10.1111/j.1471-4159.2010.06624.x
关键词
cerebellar granule neurons; guanosine; hypoxia; neuroprotection; pheochromocytoma cells; protein kinase C-related kinase 1
资金
- Austrian FWF [P19578-B05]
Exposure of pheochromocytoma cells to hypoxia (1% O-2) 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.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据