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标题：Phosphatidylinositol transfer protein α regulates growth and apoptosis of NIH3T3 cells involvement of a cannabinoid 1-like receptor
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作者：Martijn Schenning ; Claudia M. van Tiel ; Daniëlle van Manen 等
期刊名称：JLR Papers In Press
印刷版ISSN：0022-2275
电子版ISSN：1539-7262
出版年度：2004
卷号：45
期号：8
页码：1555-1564
DOI：10.1194/jlr.M400127-JLR200
语种：English
出版社：American Society for Biochemistry and Molecular Biology
摘要：Mouse fibroblast cells overexpressing phosphatidylinositol transfer protein α [PI-TPα; sense PI-TPα (SPIα) cells] show a significantly increased rate of proliferation and an extreme resistance toward ultraviolet- or tumor necrosis factor-α-induced apoptosis. The conditioned medium (CM) from SPIα cells or the neutral lipid extract from CM stimulated the proliferation of quiescent wild-type NIH3T3 cells. CM was also highly effective in increasing resistance toward induced apoptosis in both wild-type cells and the highly apoptosis-sensitive SPIβ cells (i.e., wild-type cells overexpressing PI-TPβ). CM from SPIα cells grown in the presence of NS398, a specific cyclooxygenase-2 (COX-2) inhibitor, expressed a diminished mitogenic and antiapoptotic activity. This strongly suggests that at least one of the bioactive factor(s) is an eicosanoid. In accordance, SPIα cells express enhanced levels of COX-1 and COX-2. The antiapoptotic activity of CM from SPIα cells tested on SPIβ cells was inhibited by ∼50% by pertussis toxin and suramin as well as by SR141716A, a specific antagonist of the cannabinoid 1 receptor. These inhibitors had virtually no effect on the COX-2-independent antiapoptotic activity of CM from SPIα cells.. The latter results imply that PI-TPα mediates the production of a COX-2-dependent eicosanoid that activates a G-protein-coupled receptor, most probably a cannabinoid 1-like receptor.