Phospholipase A2 is involved in muscarinic receptor-mediated sAPPα release independently of cyclooxygenase or lypoxygenase activity in SH-SY5Y cells
Phospholipase A2 is involved in muscarinic receptor-mediated sAPPα release independently of cyclooxygenase or lypoxygenase activity in SH-SY5Y cells
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DOI：
10.1016/j.neulet.2005.12.014
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发表时间：
2006-04-24
影响因子：
2.5
通讯作者：
Kim, HJ
中科院分区：
文献类型：
--
作者：
Cho, HW;Kim, JH;Kim, HJ
可溶性淀粉样前体蛋白α (sAPP α)的释放受多种外部和内部信号的高度调节，是α分泌酶在APP的P淀粉样肽区域裂解过程中产生的。由于有证据表明炎症过程参与阿尔茨海默病的病理和APP的形成，我们研究了磷脂酶A(2) （PLA(2)）途径及其下游环加氧酶（COX）和脂氧合酶（LOX）途径在SH-SY5Y细胞中参与调节毒毒碱受体激活诱导的sAPPa释放。使用检测sAPP α的单克隆6E10抗体分析释放到培养基中的sAPP的数量。用PLA2抑制剂manoalide处理，阻断oxoM（毒蕈碱受体激动剂）刺激的sAPP α的释放，并且非选择性PLA2激活剂mellitin增加了毒蕈碱受体介导的sAPPa释放。COX和LOX抑制剂抑制外源性aa诱导的sAPPa释放，但上调基础组成型sAPP α释放。然而，COX或LOX抑制剂治疗未能显著改变oxom刺激的sAPP α释放，此外，毒蕈碱受体激活抑制了aa刺激的COX活性。我们的研究结果表明，毒瘤碱受体激活诱导的sAPP α释放受AA通过PLA2激活产生的调节，独立于COX和LOX活性，但COX和LOX途径可能参与了sAPP α的组成释放。2005爱思唯尔爱尔兰有限公司版权所有。
The release of soluble amyloid precursor protein alpha (sAPP alpha), produced during alpha-secretase processing by cleavage within the P amyloid peptide domain of APP, is highly regulated by several external and internal signals. Because evidence suggests the involvement of inflammatory processes in the pathology of Alzheimer's disease and APP formation, we examined the involvement of the phospholipase A(2) (PLA(2)) pathway and of its downstream cyclooxygenase, (COX) and lipoxygenase (LOX) pathways in the regulation of sAPPa, release induced by muscarinic receptor activation in SH-SY5Y cells. The amount of sAPP released into the culture medium was analyzed using a monoclonal 6E10 antibody detecting sAPP alpha. Treatment with the PLA2 inhibitor, manoalide, blocked the release of oxoM (muscarinic receptor agonist)-stimulated sAPP alpha, and the muscarinic receptor-mediated sAPPa release was increased by the non-selective PLA2 activator mellitin. COX and LOX inhibitors inhibited exogenous AA-induced sAPPa release, but upregulated basal constitutive sAPP alpha release. However, treatment with COX or LOX inhibitors failed to significantly change oxoM-stimulated sAPP alpha release, and furthermore, muscarinic receptor activation inhibited AA-stimulated COX activity. Our results suggest that sAPP alpha release induced by muscarinic receotor activation is regulated by AA generation via PLA2 activation independently of COX and LOX activities, but that the COX and LOX pathways are possibly involved in the constitutive release of sAPP alpha. (c) 2005 Elsevier Ireland Ltd. All rights reserved.