1-(CARBOXYMETHYLTHIO)TETRADECANE ATTENUATES PDGF-INDUCED AND TPA-INDUCED C-FOS MESSENGER-RNA EXPRESSION AND INCREASES THE FORMATION OF PHOSPHATIDYLETHANOLAMINE WITH A SHIFT FROM LESS TO MORE POLAR MOLECULAR-SPECIES IN C3H 1OT1/2 CELLS/

1-(Carboxymethylthio)tetradecane caused C3H/10T1/2Cl8 and C3H/10T1/2Cl 16 to incorporate 10 times more [P-32]P-i into diacylphosphatidylethan olamine than control This 3-thia fatty acid caused a shift in incorpor ation of P-32-radioactivity into phosphatidylethanolamine species from species with long to species with short HPLC elution times. The incre ase in P-32-labeling was parallelled by a change in the apparent mass of phosphatidylethanolamine to a higher proportion of molecular specie s with short elution times than with long elution times. 1-(Carboxymet hylthio)tetradecane caused loss of molecular species containing stearo yl groups. These results indicate that culturing the cells with 1-(car boxymethylthio)tetradecane causes looser packing and an increase in fl uidity of the diacylphosphatidylethanolamine molecules in the membrane s. 12-O-tetradecanoyl phorbol-13-acetate (TPA), platelet-derived growt h factor (PDGF)BB, or PDGF-AA stimulation of 1-(carboxymethylthio)tetr adecane-treated cells resulted in decreased maximal levels of c-fos mR NA expression, indicating attenuation of signal transduction Compared to cells not treated, the levels of both PDGF-alpha and PDGF-beta rece ptors were lower while GTPase-activating protein and phospholipase C-g amma levels were not altered in C3H/10T1/2Cl8 and C3H/10T1/2Cl16 cells cultured in the presence of 1-(carboxy methylthio)tetradecane. Our da ta demonstrate that 1-(carboxymethylthio)tetradecane-mediated changes in phospholipid structure and composition may affect PDGF-and TPA-medi ated c-fos gene regulation in fibroblasts. (C) 1997 Academic Press.