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.
Tripathi
Y B
YB
Department of Pharmacology, University of Missouri, School of Medicine, Columbia 65212.
Kandala
J C
JC
Guntaka
R V
RV
Lim
R W
RW
Shukla
S D
SD
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