Secretory phospholipase A(2) induces apoptosis via a mechanism involving ceramide generation.
Secretory phospholipase A(2) induces apoptosis via a mechanism involving ceramide generation.
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DOI：
10.1016/s1388-1981(02)00122-1
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发表时间：
2002-04
期刊：
影响因子：
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通讯作者：
Sheng Zhao;Xiao-Yan Du;M. Chai;Jun-Song Chen;Yuanli Zhou;Jianguo Song
中科院分区：
文献类型：
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作者：
Sheng Zhao;Xiao-Yan Du;M. Chai;Jun-Song Chen;Yuanli Zhou;Jianguo Song
分泌型磷脂酶A2（sPLA 2）在细胞信号转导和各种生物学事件中起重要作用。本研究探讨了纯化的sPLA 2对MV 1 Lu细胞的生物学效应及其可能的信号转导机制。纯化了3种蛇毒sPLA 2，并通过[3 H]-肉豆蔻酸标记细胞制备的不同脂质底物，测定其对花生四烯酸（AA）释放的诱导作用，研究了其酶活性。纯化的sPLA 2以剂量和时间依赖性方式诱导Mv 1 Lu细胞凋亡，并与细胞内神经酰胺水平的快速增加相关。在用外源性神经酰胺类似物C2-和C8-神经酰胺处理的Mv 1 Lu细胞中观察到类似的凋亡效应。此外，用鞘磷脂酶（SMase）处理细胞，降低细胞内SM水平，增强了对sPLA 2的凋亡反应。sPLA 2s对缓激肽诱导的磷脂酶D（PLD）活性也有抑制作用，这种抑制作用可被外源性神经酰胺所模拟。我们的数据表明，sPLA 2诱导细胞凋亡的机制，包括增加神经酰胺的产生。
Secretory phospholipase A2(sPLA2) plays important roles in cellular signaling and various biological events. In this study, we examined the biological effects and the potential signaling mechanism of purified sPLA2in MV1Lu cells. Three types of snake venom sPLA2were purified and their enzymatic activities were characterized by using various lipid substrates prepared from [3H]-myristate-labeled cells and by determining their effects on the induction of arachidonic acid (AA) release. The purified sPLA2induced apoptosis in Mv1Lu cells in a dose- and time-dependent manner, and was associated with a rapid increase in the intracellular ceramide level. Similar apoptotic effects were observed in Mv1Lu cells treated with exogenous ceramide analog, C2- and C8-ceramide. Moreover, treatment of cells with sphingomyelinase (SMase), which reduced the intracellular SM level, enhanced the apoptotic response to sPLA2s. sPLA2s also displayed an inhibitory effect on bradykinin-induced phospholipase D (PLD) activity, which can be imitated by exogenous ceramide. Our data indicate that sPLA2induces cell apoptosis via a mechanism involving increased ceramide generation.