Antioxidants stimulate transcriptional activation of the c-fos gene by multiple pathways in human fetal lung fibroblasts (WI-38)
✍ Scribed by Bart Keogh; R. G. Allen; Maria Tresini; John J. Furth; Vincent J. Cristofalo
- Publisher
- John Wiley and Sons
- Year
- 1998
- Tongue
- English
- Weight
- 236 KB
- Volume
- 176
- Category
- Article
- ISSN
- 0021-9541
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✦ Synopsis
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-a from the cytosol to the membrane. These results suggest that increasing the intracellular reducing potential induces c-fos expression through multiple pathways.