1-(Carboxymethylthio)tetradecane attenuates PDGF- and TPA-induced c-fos mRNA expression and increases the formation of phosphatidylethanolamine with a shift from less to more polar molecular species in C3H/10T1/2 cells.
1-(Carboxymethylthio)tetradecane caused C3H/10T1/2Cl8 and C3H/10T1/2Cl16 to incorporate 10 times more [32P]Pi into diacylphosphatidylethanolamine than control. This 3-thia fatty acid caused a shift in incorporation of 32P-radioactivity into phosphatidylethanolamine species from species with long to species with short HPLC elution times. The increase in 32P-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-fos mRNA expression, indicating attenuation of signal transduction. Compared to cells not treated, the levels of both PDGF-alpha and PDGF-beta receptors were lower while GTPase-activating protein and phospholipase C-gamma levels were not altered in C3H/10T1/2Cl8 and C3H/10T1/2Cl16 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-fos gene regulation in fibroblasts.
Helleland
C
C
Department of Molecular Biology, University of Bergen, Norway.
Eiane
S A
SA
Berge
R K
RK
Holmsen
H
H
Lillehaug
J R
JR
D000818:Animals; D000925:Anticoagulants / Q000494:pharmacology; D000077214:Becaplermin; D015153:Blotting, Western; D002273:Carcinogens / Q000494:pharmacology*; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D015870:Gene Expression / Q000187:drug effects; D051379:Mice; D008809:Mice, Inbred C3H; D010712:Phosphatidic Acids / Q000378:metabolism; D010714:Phosphatidylethanolamines / Q000737:chemistry / Q000378:metabolism*; D010758:Phosphorus / Q000378:metabolism; D010761:Phosphorus Radioisotopes / Q000378:metabolism; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology*; D011233:Precipitin Tests; D016760:Proto-Oncogene Proteins c-fos / Q000032:analysis / Q000235:genetics*; D020574:Proto-Oncogene Proteins c-sis; D012333:RNA, Messenger / Q000378:metabolism; D013440:Sulfides / Q000494:pharmacology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*; D013997:Time Factors
D000925:Anticoagulants; D002273:Carcinogens; D010712:Phosphatidic Acids; D010714:Phosphatidylethanolamines; D010761:Phosphorus Radioisotopes; D010982:Platelet-Derived Growth Factor; D016760:Proto-Oncogene Proteins c-fos; D020574:Proto-Oncogene Proteins c-sis; D012333:RNA, Messenger; D013440:Sulfides; C075278:platelet-derived growth factor A; D000077214:Becaplermin; D010758:Phosphorus; C062078:1-(carboxymethylthio)tetradecane; D013755:Tetradecanoylphorbol Acetate