1-(Carboxymethylthio)tetradecane Attenuates PDGF- and TPA-Induced c-fosmRNA Expression and Increases the Formation of Phosphatidylethanolamine with a Shift from Less to More Polar Molecular Species in C3H/10T[formula omitted] Cells

Abstract

1-(Carboxymethylthio)tetradecane caused C3H/10T12Cl8 and C3H/10T12Cl16 to incorporate 10 times more [32P]Piinto diacylphosphatidylethanolamine than control. This 3-thia fatty acid caused a shift in incorporation of32P-radioactivity into phosphatidylethanolamine species from species with long to species with short HPLC elution times. The increase in32P-labeling was parallelled by a change in the apparent mass of phosphatidylethanolamine to a higher proportion of molecular species with short elution times than with long elution times. 1-(Carboxymethylthio)tetradecane caused loss of molecular species containing stearoyl groups. These results indicate that culturing the cells with 1-(carboxymethylthio)tetradecane causes looser packing and an increase in fluidity of the diacylphosphatidylethanolamine molecules in the membranes. 12-O-tetradecanoyl phorbol-13-acetate (TPA), platelet-derived growth factor (PDGF)-BB, or PDGF-AA stimulation of 1-(carboxymethylthio)tetradecane-treated cells resulted in decreased maximal levels of c-fosmRNA expression, indicating attenuation of signal transduction. Compared to cells not treated, the levels of both PDGF-α and PDGF-β receptors were lower while GTPase-activating protein and phospholipase C-γ levels were not altered in C3H/10T12Cl8 and C3H/10T12Cl16 cells cultured in the presence of 1-(carboxymethylthio)tetradecane. Our data demonstrate that 1-(carboxymethylthio)tetradecane-mediated changes in phospholipid structure and composition may affect PDGF-and TPA-mediated c-fosgene regulation in fibroblasts.