Apoptotic effect of sphingosine 1-phosphate and increased sphingosine 1-phosphate hydrolysis on mesangial cells cultured at low cell density
Apoptotic effect of sphingosine 1-phosphate and increased sphingosine 1-phosphate hydrolysis on mesangial cells cultured at low cell density
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DOI：
10.1074/jbc.m108933200
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发表时间：
2002-04-12
影响因子：
4.8
通讯作者：
Salles, JP
中科院分区：
文献类型：
--
作者：
Gennero, I;Fauvel, J;Salles, JP
脂质介质鞘氨醇1-磷酸（SIP）可以改变系膜细胞的增殖过程中的病理生理过程。在这里，S1 P刺激大鼠肾小球系膜细胞的增殖和磷酸化的MAPK在亚汇合细胞密度。这两种作用都被百日咳毒素处理抑制。系膜细胞表达内皮分化基因家族的几种SIP受体：EDG-1、-3、-5和-8。相反，S1 P在低细胞密度（2 × 10（4）cells/cm（2））下诱导凋亡，这通过流式细胞术和Hoechst染色证实。在静止或生长的细胞中也观察到细胞凋亡，溶血磷脂酸或血小板衍生生长因子不能逆转。SIP增强SAPKs的磷酸化。用[P-33] S1 P、[H-3] S1 P和[H-3]鞘氨醇孵育证明SIP水解增加，导致细胞内鞘氨醇水平增加和S1 P水平降低。还观察到总神经酰胺水平的升高;然而，神经酰胺并不来源于[H-3]鞘氨醇，伏马菌素B不抑制S1 P诱导的细胞凋亡，排除了从头神经酰胺合成参与细胞凋亡。因此，我们认为鞘氨醇的积累和减少S1 P是主要负责S1 P诱导的细胞凋亡。总之，低密度系膜细胞与S1 P孵育会导致细胞凋亡，这可能是由于S1 P水解增加所致。
The lipid mediator sphingosine 1-phosphate (SIP) may alter the proliferation of mesangial cells during pathophysiological processes. Here, S1P stimulated proliferation of rat mesangial cells and phosphorylation of MAPKs at subconfluent cell density. Both effects were inhibited by pertussis toxin treatment. Mesangial cells expressed several SIP receptors of the endothelial differentiation gene family: EDG-1, -3, -5, and -8. Conversely, S1P induced apoptosis at low cell density (2 X 10(4) cells/cm(2)), which was demonstrated by flow cytometry and Hoechst staining. Apoptosis was observed also in quiescent or growing cells and was not reverted by lysophosphatidic acid or platelet-derived growth factor. SIP enhanced phosphorylation of SAPKs. Incubation with [P-33]S1P, [H-3]S1P, and [H-3]sphingosine demonstrated increased SIP hydrolysis, resulting in enhanced intracellular sphingosine levels and decreased S1P levels. A rise in total ceramide levels was also observed; however, ceramide did not originate from [H-3]sphingosine, and S1P-induced apoptosis was not inhibited by fumonisin B, precluding involvement of de novo ceramide synthesis in apoptosis. Therefore, we suggest that sphingosine accumulation and decreased S1P are primarily responsible for S1P-induced apoptosis. In conclusion, incubation of low-density mesangial cells with S1P results in apoptosis, presumably due to increased S1P hydrolysis.