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Antioxidants stimulate transcriptional activation of the c‐fos gene by multiple pathways in human fetal lung fibroblasts (WI‐38)
Author(s) -
Keogh Bart,
Allen R. G.,
Tresini Maria,
Furth John J.,
Cristofalo Vincent J.
Publication year - 1998
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/(sici)1097-4652(199809)176:3<624::aid-jcp19>3.0.co;2-z
Subject(s) - c fos , trolox , protein kinase c , chemistry , nordihydroguaiaretic acid , gene expression , glutathione , cytosol , intracellular , transcription factor , microbiology and biotechnology , signal transduction , biochemistry , biology , gene , antioxidant , enzyme , arachidonic acid , dpph
We have examined the effects of three structurally distinct antioxidants (N‐acetylcysteine [NAC], Trolox C [a water‐soluble vitamin E derivative], and nordihydroguaiaretic acid [NGA]) on the expression of the c‐fos gene over a 2‐hour period. Determination of cellular glutathione concentration (the primary determinant of the cellular redox state) over the same time‐course verifies that all the compounds studied cause an increase in cellular reduction potential. The level of c‐fos messenger RNA increased rapidly in response to micromolar concentrations of these compounds, reaching a peak in 30–60 minutes. Induction of c‐fos expression by these antioxidants is at least partly due to an increase in transcription, as determined by nuclear run‐on assay. Down regulation of protein kinase C (PKC) by pretreatment for 24 hours with 500 nm PMA prevents induction by subsequent stimulation with either PMA or NGA. NAC induction of c‐fos is unaffected by PMA pretreatment, while Trolox C superinduced c‐fos following PMA pretreatment. None of these treatments stimulated translocation of PKC‐α from the cytosol to the membrane. These results suggest that increasing the intracellular reducing potential induces c‐fos expression through multiple pathways. J. Cell. Physiol. 176:624–633, 1998. © 1998 Wiley‐Liss, Inc.