INDUCTION OF C-FOS AND C-JUN GENE-EXPRESSION BY PHENOLIC ANTIOXIDANTS

被引:73
作者
CHOI, HS [1 ]
MOORE, DD [1 ]
机构
[1] MASSACHUSETTS GEN HOSP,DEPT MOLEC BIOL,BOSTON,MA 02114
关键词
D O I
10.1210/me.7.12.1596
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
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.
引用
收藏
页码:1596 / 1602
页数:7
相关论文
共 39 条
[1]   REDOX REGULATION OF FOS AND JUN DNA-BINDING ACTIVITY INVITRO [J].
ABATE, C ;
PATEL, L ;
RAUSCHER, FJ ;
CURRAN, T .
SCIENCE, 1990, 249 (4973) :1157-1161
[2]  
AMSTAD PA, 1992, CANCER RES, V52, P3952
[3]   THE JUN PROTO-ONCOGENE IS POSITIVELY AUTOREGULATED BY ITS PRODUCT, JUN/AP-1 [J].
ANGEL, P ;
HATTORI, K ;
SMEAL, T ;
KARIN, M .
CELL, 1988, 55 (05) :875-885
[4]   THE ROLE OF JUN, FOS AND THE AP-1 COMPLEX IN CELL-PROLIFERATION AND TRANSFORMATION [J].
ANGEL, P ;
KARIN, M .
BIOCHIMICA ET BIOPHYSICA ACTA, 1991, 1072 (2-3) :129-157
[5]  
Ausubel FM, 1993, CURRENT PROTOCOLS MO
[6]   MULTIHORMONAL REGULATION OF THE HUMAN, RAT, AND BOVINE GROWTH-HORMONE PROMOTERS - DIFFERENTIAL-EFFECTS OF 3',5'-CYCLIC ADENOSINE-MONOPHOSPHATE, THYROID-HORMONE, AND GLUCOCORTICOIDS [J].
BRENT, GA ;
HARNEY, JW ;
MOORE, DD ;
LARSEN, PR .
MOLECULAR ENDOCRINOLOGY, 1988, 2 (09) :792-798
[7]  
CHOI HS, 1990, J BIOL CHEM, V265, P18005
[8]  
CRAWFORD D, 1988, ONCOGENE, V3, P27
[9]   FOS AND JUN - THE AP-1 CONNECTION [J].
CURRAN, T ;
FRANZA, BR .
CELL, 1988, 55 (03) :395-397
[10]   CHARACTERIZATION OF SAP-1, A PROTEIN RECRUITED BY SERUM RESPONSE FACTOR TO THE C-FOS SERUM RESPONSE ELEMENT [J].
DALTON, S ;
TREISMAN, R .
CELL, 1992, 68 (03) :597-612