Neurotrophins Rescue Cerebellar Granule Neurons from Oxidative Stress-Mediated Apoptotic Death: Selective Involvement of Phosphatidylinositol 3-Kinase and the Mitogen-Activated Protein Kinase Pathway

来自 Wiley

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作者：

Stephen，D.，Skaper，Maura，Floreani，Alessandro，Negro，Laura，Facci，Pietro

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摘要：

Cerebellar granule neurons maintained in medium containing serum and 25 mM K+ reliably undergo an apoptotic death when switched to serum-free medium with 5 mM K+. New mRNA and protein synthesis and formation of reactive oxygen intermediates are required steps in K+ deprivation-induced apoptosis of these neurons. Here we show that neurotrophins, members of the nerve growth factor gene family, protect from K+/serum deprivation-induced apoptotic death of cerebellar granule neurons in a temporally distinct manner. Switching granule neurons, on day in vitro (DIV) 4, 10, 20, 30, or 40, from high-K+ to low-K+/serum-free medium decreased viability by >50% when measured after 30 h. Treatment of low-K+ granule neurons at DIV 4 with nerve growth factor, brain-derived neurotrophic factor (BDNF), neurotrophin-3, or neurotrophin-4/5 (NT-4/5) demonstrated concentration-dependent (1–100 ng/ml) protective ef

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关键词：

Oxidative stress Apoptosis Neurotrophins Neuroprotection Signal transduction Melatonin Glutathione