The anti-apoptotic activity associated with phosphatidylinositol transfer protein α activates the MAPK and Akt/PKB pathway
The anti-apoptotic activity associated with phosphatidylinositol transfer protein α activates the MAPK and Akt/PKB pathway
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DOI：
10.1016/j.bbamcr.2008.04.014
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发表时间：
2008-10-01
影响因子：
5.1
通讯作者：
Snoek, Gerry T.
中科院分区：
文献类型：
--
作者：
Schenning, Martijn;Goedhart, Joachim;Snoek, Gerry T.
与来自野生型NIH 3 T3（wtNIH 3 T3）细胞的条件培养基（CM）相比，来自过表达磷脂酰肌醇转移蛋白a（PI-TP α; SPI α细胞）的小鼠NIH 3 T3成纤维细胞的条件培养基（CM）显示出增加的抗凋亡活性。如前所述，抗凋亡活性通过激活G蛋白偶联受体起作用，最可能是大麻素1（CB 1）样受体，因为该活性被百日咳毒素和利莫那班阻断[M. Schenning，C.M.货车蒂尔，D.货车马南Stam，B.M. Gadella，K.W.维尔茨和G.T. Snoek，Phosphatidylinositol transfer protein alpha regulates growth and apoptosis of NIH3T3 cells：involvement of a cannabinoid 1-like receptor，J. Lipid Res.45（2004）1555-1564]。CB 1受体似乎在小鼠成纤维细胞中表达，表达水平的顺序为SPI α> wtNIH 3 T3> SPI β细胞（即野生型细胞过度表达PI-TP β）。在将SPI β细胞与PI-TP α依赖性抗凋亡因子孵育后，ERK/MAP激酶和Akt/PKB途径均以CB 1受体依赖性方式激活，如Western印迹所示。此外，通过共聚焦激光扫描显微镜观察，EYFP-ERK 2易位至细胞核也显示了ERK 2的激活。抗凋亡转录因子NF-κ B的随后激活与对UV诱导的凋亡的增加的抗性一致。另一方面，来自SPI α细胞的CM的受体激活与磷脂酶C激活无关，因为YFP标记的蛋白激酶C的C2结构域没有移位到SPI β细胞的质膜，如通过共聚焦激光扫描显微镜观察到的。(c)2008 Elsevier B. V.保留所有权利。
The conditioned medium (CM) from mouse NIH3T3 fibroblast cells overexpressing phosphatidylinositol transfer protein a (PI-TP alpha; SPI alpha cells) demonstrates an increased anti-apoptotic activity compared with CM from wild type NIH3T3 (wtNIH3T3) cells. As previously shown, the anti-apoptotic activity acts by activating a G protein-coupled receptor, most probably a cannabinoid 1 (CB1)-like receptor as the activity was blocked by both pertussis toxin and rimonabant [M. Schenning, C.M. van Tiel, D. Van Manen, J.C. Stam, B.M. Gadella, K.W. Wirtz and G.T. Snoek, Phosphatidylinositol transfer protein alpha regulates growth and apoptosis of NIH3T3 cells: involvement of a cannabinoid 1-like receptor, J. Lipid Res. 45 (2004) 1555-1564]. The CB1 receptor appears to be expressed in mouse fibroblast cells, at levels in the order SPI alpha > wtNIH3T3 > SPI beta cells (i.e. wild type cells overexpressing PI-TP beta). Upon incubation of SPI beta cells with the PI-TP alpha-dependent anti-apoptotic factors, both the ERK/MAP kinase and the Akt/PKB pathway are activated in a CB1 receptor dependent manner as shown by Western blotting. In addition, activation of ERK2 was also shown by EYFP-ERK2 translocation to the nucleus, as visualized by confocal laser scanning microscopy. The subsequent activation of the anti-apoptotic transcription factor NF-kappa B is in line with the increased resistance towards UV-induced apoptosis. On the other hand, receptor activation by CM from SPI alpha cells was not linked to phospholipase C activation as the YFP-labelled C2-domain of protein kinase C was not translocated to the plasma membrane of SPI beta cells as visualized by confocal laser scanning microscopy. (c) 2008 Elsevier B.V. All rights reserved.