Platelet activating factor induces expression of early response genes c-fos and TIS-1 in human epidermoid carcinoma A-431 cells.
The effect of platelet activating factor (PAF) on the induction of early response genes was investigated in A-431 cells (human epidermal carcinoma cells). PAF induced a transient expression of c-fos and TIS-1 mRNA in a time- and dose-dependent manner. As low as 10(-10) M PAF caused detectable expression of these genes with a maximum observed at 10(-7) M. In the presence of cycloheximide, increases in the gene expression were noticeable at 20 min and peaked between 30-60 min. A lack of induction with lyso-PAF, an inactive PAF metabolite, confirmed the specificity of PAF towards this expression. The cells pretreated with CV-6209, a PAF receptor antagonist, did not show any induction of these genes by PAF. It is concluded that PAF causes induction of the early response genes c-fos and TIS-1 in a structurally specific and receptor dependent manner. This finding offers a new role for PAF at the nuclear level and may have important implications in the long term effects of PAF in pathophysiological conditions.
Department of Pharmacology, University of Missouri, School of Medicine, Columbia 65212.
Y B
YB
Tripathi
J C
JC
Kandala
R V
RV
Guntaka
R W
RW
Lim
S D
SD
Shukla
D003513:Cycloheximide / Q000494:pharmacology; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D016762:Genes, fos; D006801:Humans; D007700:Kinetics; D010972:Platelet Activating Factor / Q000031:analogs & derivatives / Q000494:pharmacology*; D011726:Pyridinium Compounds / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012334:RNA, Neoplasm / Q000235:genetics / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014407:Tumor Cells, Cultured
C029271:O-deacetyl platelet activating factor; D010972:Platelet Activating Factor; D011726:Pyridinium Compounds; D012333:RNA, Messenger; D012334:RNA, Neoplasm; C053321:CV 6209; D003513:Cycloheximide; D013755:Tetradecanoylphorbol Acetate