Protein phosphatase type 2Cα and 2Cβ are involved in fatty acid-induced apoptosis of neuronal and endothelial cells
Protein phosphatase type 2Cα and 2Cβ are involved in fatty acid-induced apoptosis of neuronal and endothelial cells
复制标题
DOI：
10.1007/s10495-006-6982-1
复制
发表时间：
2006-07-01
期刊：
影响因子：
7.2
通讯作者：
Krieglstein, Josef
中科院分区：
文献类型：
--
作者：
Schwarz, Stephanie;Hufnagel, Birgit;Krieglstein, Josef
不饱和脂肪酸具有特殊的结构特征，在体外生理浓度下能够激活丝氨酸/苏氨酸蛋白磷酸酶2C亚型(PP2C)的α和β亚型。这些化合物还可以诱导神经细胞和内皮细胞的凋亡。在这项研究中，我们进一步分析了这种显著的相关性，并试图阐明PP2C的激活和诱导凋亡之间是否存在因果关系。我们利用RNA干扰分别在SH-SY5Y细胞和HUVECs中同时下调PP2Cα和PP2Cβ。这种下调是暂时的。油酸(18：1，顺-Delta(9))处理SH-SY5Y细胞或HUVECs可诱导细胞凋亡，且呈时间和浓度依赖性。在这两种情况下，PP2C水平降低的细胞对油酸诱导的细胞损伤的敏感性较低。综上所述，我们的结果表明，不饱和脂肪酸激活PP2C实际上会导致神经细胞和内皮细胞的凋亡。
Unsaturated fatty acids with special structural features have been shown to activate serine/threonine protein phosphatase type 2C (PP2C) isoforms alpha and beta at physiological Mg2+-concentrations in vitro. These compounds also induce apoptosis in neuronal and endothelial cells. In this study we further analysed this striking correlation and tried to elucidate whether or not there is a causative relationship between activation of PP2C and induction of apoptosis.We employed RNA interference to simultaneously knock down PP2C alpha and PP2C beta in SH-SY5Y cells or HUVECs, respectively. This downregulation was transient. Treatment of SH-SY5Y cells or HUVECs with oleic acid (18:1, cis-Delta(9)) caused apoptosis in a time- and concentration-dependent manner. In both cases, cells with reduced PP2C-levels were less susceptible to oleic acid-induced cell damage.In conclusion, our results demonstrate that PP2C activation by unsaturated fatty acids actually causes apoptosis in neuronal and endothelial cells.