Induction of c-fos and c-jun gene expression by phenolic antioxidants.
We have found that phenolic antioxidants specifically induce expression of the c-fos and c-jun protooncogenes. After treatment of quiescent human hepatoma HepG2 cells with butylated hydroxytoluene, butylated hydroxyanisole, or other phenolic antoxidants, the levels of c-fos and c-jun mRNAs are substantially increased. This response is antioxidant specific, dose dependent, and transient, with maximal levels at 3-6 h. The antioxidant-specific induction of c-fos/CAT promoter constructs in transient transfections indicates that at least a portion of this response is transcriptional. Deletions and point mutations map sequences required for the antioxidant response of the c-fos promoter to the serum response element. The antioxidant-specific induction of expression directed by a reporter plasmid containing four AP-1 sites and the induction of AP-1 DNA-binding activity confirm previous results indicating that antioxidant treatment increases AP-1 activity.
Choi
H S
HS
Department of Molecular Biology, Massachusetts General Hospital, Boston 02114.
Moore
D D
DD
D000975:Antioxidants / Q000494:pharmacology*; D001483:Base Sequence; D002083:Butylated Hydroxyanisole / Q000494:pharmacology; D002084:Butylated Hydroxytoluene / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects*; D016762:Genes, fos / Q000187:drug effects*; D016758:Genes, jun / Q000187:drug effects*; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D008969:Molecular Sequence Data; D010084:Oxidation-Reduction; D010636:Phenols / Q000494:pharmacology*; D011401:Promoter Regions, Genetic / Q000187:drug effects; D016755:Proto-Oncogene Proteins c-jun / Q000378:metabolism; D013329:Structure-Activity Relationship
D000975:Antioxidants; D010636:Phenols; D016755:Proto-Oncogene Proteins c-jun; D002084:Butylated Hydroxytoluene; D002083:Butylated Hydroxyanisole; D006861:Hydrogen Peroxide