Phosphatidylinositol transfer protein α regulates growth and apoptosis of NIH3T3 cells

Abstract

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.

Keywords

• cyclooxygenase 2
• proliferation
• eicosanoids