Comparison of inhibitory effects of brain-derived neurotrophic factor and insulin-like growth factor on low potassium-induced apoptosis and activation of p38 MAPK and c-Jun in cultured cerebellar gran

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• 作者：Yamagishi ; Satoru ; Matsumoto ; Tomoya ; Yokomaku ; Daisaku ; Hatanaka ; Hiroshi ; Shimoke ; Koji ; et. al.
• 关键词：Development and regeneration ; neurotrophic factors ; receptors and cellular mechanisms ; BDNF ; IGF-1 ; p38 ; c-Jun ; PI3-K
• 刊名：Molecular Brain Research
• 出版年：2003
• 出版时间：November 26, 2003
• 年：2003
• 卷：119
• 期：2
• 页码：184-191
• 全文大小：402 K

文摘

On cell maturation following culture in medium containing 26 mM potassium (high K⁺; HK), a change to medium containing 5 mM potassium (low K⁺; LK) rapidly induces apoptosis in rat cerebellar granule neurons. Brain-derived neurotrophic factor (BDNF) and insulin-like growth factor-1 (IGF-1) have survival-promoting effects on the neurons via PI3-K. However, it remains unclear how they prevent the apoptosis in the pathway downstream of phosphatidylinositol-3 kinase (PI3-K). Recently, we have reported that PI3-K-ASK1 pathway is involved in signal-transduction to p38 MAPK (p38)-c-Jun pathway. Here we found that IGF-1 had a greater survival-promoting effect than BDNF, and activated PI3-K to a higher level and maintained the level for a longer time. BDNF and IGF-1 suppressed the activation of p38 and c-Jun, but not of c-Jun N-terminal kinase (JNK), caused by lowering the potassium concentration. The inhibitory effects of IGF-1 were much greater than those of BDNF. In addition, LY294002, a specific inhibitor of PI3-K, cancelled the inhibitory effects of BDNF and IGF-1. These results suggest that the greater inhibitory effects of IGF-1 than BDNF, on activation of p38 and c-Jun and apoptosis, are caused by the higher level of PI3-K activation during LK-induced apoptosis of cultured cerebellar granule neurons.