AT2 receptor stimulation induces generation of ceramides in PC12W cells
AT2 receptor stimulation induces generation of ceramides in PC12W cells
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DOI：
10.1016/s0014-5793(98)01675-5
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发表时间：
1999-01-22
期刊：
影响因子：
3.5
通讯作者：
Unger, T
中科院分区：
文献类型：
--
作者：
Gallinat, S;Busche, S;Unger, T
血管紧张素AT(2)受体与再生和细胞凋亡都有关系。为了进一步研究AT(2)受体诱导PC12W细胞程序性死亡的分子机制，我们通过HPTLC分析研究了血管紧张素II （ANG II）对神经酰胺水平的影响。我们可以证明，ANG II的时间依赖性（1-10小时）和剂量依赖性(10（-8)-5x10(-6) M）使神经酰胺水平最高提高了175%，但不影响鞘磷脂的降解。ANG II的作用是由AT(2)受体介导的，因为它们通过与AT(2)受体拮抗剂PD123177 （10(-5) M）共培养完全消除，而不是由AT(1)受体拮抗剂氯沙坦（10(-5)M）介导。这些数据提示了一种新的信号转导途径到AT(2)受体导致神经元细胞凋亡。(C) 1999年欧洲生化学会联合会。
The angiotensin AT(2) receptor has been implicated in both regeneration and apoptosis. To further investigate the molecular mechanisms leading to AT(2) receptor-induced programmed cell death in PC12W cells we studied the effects of angiotensin II (ANG II) on ceramide levels by HPTLC analysis. We could demonstrate that ANG II time- (1-10 h) and dose-dependently (10(-8)-5x10(-6) M) increased ceramide levels by maximally 175% but did not affect sphingomyelin degradation, The ANG II effects,were mediated by AT(2) receptors since they were completely abolished by co-incubation with the AT(2) receptor antagonist, PD123177 (10(-5) M), but not by the AT(1) receptor antagonist, losartan (10(-5) M). These data suggest a novel signal transduction pathway to the AT(2) receptor leading to apoptosis in neuronal cells. (C) 1999 Federation of European Biochemical Societies.