A novel neurotrophic role of secretory phospholipases A2 for cerebellar granule neurons
A novel neurotrophic role of secretory phospholipases A2 for cerebellar granule neurons
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DOI：
10.1016/j.febslet.2005.03.092
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发表时间：
2005-05-09
期刊：
影响因子：
3.5
通讯作者：
Kitamoto, K
中科院分区：
文献类型：
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作者：
Arioka, M;Cheon, SH;Kitamoto, K
培养的小脑颗粒神经元（CGNs）需要膜去极化或神经营养因子，他们在体外的生存和凋亡时，剥夺这些生存促进刺激。在这里，我们发现分泌型磷脂酶A（2）s（sPLA（2）s）在钾剥夺后拯救CGN免于凋亡。神经营养作用需要sPLA（2）s的酶活性，因为sPLA（2）s的催化失活突变体不能保护CGN免于凋亡。因此，sPLA（2）保护CGN免于凋亡的能力与sPLA（2）诱导的活CGN中花生四烯酸释放的程度相关。sPLA（2）的存活促进作用被细胞外Ca 2+耗竭或L型Ca 2+通道阻断剂尼卡地平抑制，表明sPLA（2）处理后发生Ca 2+内流。在测试的哺乳动物sPLA（2）s中，只有X组sPLA（2）s显示神经营养活性，而IB组和IIA组sPLA（2）s均未显示。这些结果表明sPLA（2）在神经系统中具有一种新的、意想不到的神经营养素样作用。© 2005欧洲生物化学学会联合会。Elsevier B.V.出版，保留所有权利。
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 A(2)s (sPLA(2)s) rescue CGNs from apoptosis after potassium deprivation. The neurotrophic effect required the enzymatic activity of sPLA(2)s, since catalytically inactive mutants of sPLA(2)s failed to protect CGNs from apoptosis. Consistently, the ability of sPLA(2)s to protect CGNs from apoptosis correlated with the extent of sPLA(2)-induced arachidonic acid release from live CGNs. The survival-promoting effect of sPLA(2) was inhibited by depletion of extracellular Ca2+ or by the presence of L-type Ca2+ channel blocker nicardipine, suggesting that Ca2+ influx occurs upon sPLA(2) treatment. Among the mammalian sPLA(2)s tested, only group X sPLA(2), but not group IB nor IIA sPLA(2)s, displayed neurotrophic activity. These results suggest a novel, unexpected neurotrophin-like role of sPLA(2) in the nervous system. © 2005 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.