A novel neurotrophic role of secretory phospholipases A₂ for cerebellar granule neurons

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• 作者：Arioka ; Manabu ; Cheon ; So-hyun ; Ikeno ; Yutaka ; Nakashima ; Satoru ; Kitamoto ; Katsuhiko
• 关键词：Apoptosis ; Calcium channel ; Cerebellar granule neuron ; Neurotrophic factor ; Secretory phospholipase A₂
• 刊名：FEBS Letters
• 出版年：2005
• 出版时间：May 9, 2005
• 年：2005
• 卷：579
• 期：12
• 页码：2693-2701
• 全文大小：328 K

文摘

Cultured cerebellar granule neurons (CGNs) require membrane depolarization or neurotrophic factors for their survival in vitro and undergo apoptosis when deprived of these survival-promoting stimuli. Here, we show that secretory phospholipases A₂s (sPLA₂s) rescue CGNs from apoptosis after potassium deprivation. The neurotrophic effect required the enzymatic activity of sPLA₂s, since catalytically inactive mutants of sPLA₂s failed to protect CGNs from apoptosis. Consistently, the ability of sPLA₂s to protect CGNs from apoptosis correlated with the extent of sPLA₂-induced arachidonic acid release from live CGNs. The survival-promoting effect of sPLA₂ was inhibited by depletion of extracellular Ca²⁺ or by the presence of L-type Ca²⁺ channel blocker nicardipine, suggesting that Ca²⁺ influx occurs upon sPLA₂ treatment. Among the mammalian sPLA₂s tested, only group X sPLA₂, but not group IB nor IIA sPLA₂s, displayed neurotrophic activity. These results suggest a novel, unexpected neurotrophin-like role of sPLA₂ in the nervous system.