| First Author | Wilkinson J 4th | Year | 1998 |
| Journal | Biochem Biophys Res Commun | Volume | 253 |
| Issue | 3 | Pages | 855-8 |
| PubMed ID | 9918819 | Mgi Jnum | J:114196 |
| Mgi Id | MGI:3688483 | Doi | 10.1006/bbrc.1998.9804 |
| Citation | Wilkinson J 4th, et al. (1998) Disruption of c-Fos leads to increased expression of NAD(P)H:quinone oxidoreductase1 and glutathione S-transferase. Biochem Biophys Res Commun 253(3):855-8 |
| abstractText | Regulation of the basal and induced expression of detoxifying enzymes such as NAD(P)H:quinone oxidoreductasel (NQO1) and glutathione S-transferase (GST) by the antioxidant response element (ARE) is important for cellular protection against oxidative stress. The ARE contains AP1 and AP1-like elements and is known to bind to several leucine zipper proteins including c-Fos. Previous studies (Venugopal, R., and Jaiswal, A.K. (1996) Proc. NatL Acad. Sci. USA 93, 14960-14965) have shown that overexpression of c-Fos in transfected cells leads to repression of ARE-mediated gene expression. In the present report, we used c-Fos-/- mice and investigated the physiological (in vivo) role of c-Fos in repression of the NQO1 and GST genes expression. The analysis of enzyme activity levels showed significant increases in NQO1 and GST activities in several tissues of c-Fos-/- mice, as compared with wild type (c-Fos+/+) mice. The increases in enzyme activities were supported by Wetern analysis of respective proteins. Western analyses showed significant increases in the expression of NQO1 in kidney, liver and skin tissues of c-Fos-/- mice, as compared with wild type (c-Fos+/+) controls. Western analyses also demonstrated an increased expression of the GST Ya gene in kidney and liver tissues of the c-Fos-/-mice. These results confirm a negative (repressive) role for c-Fos in the expression of NQO1, GST Ya, and other detoxifying enzyme genes. |
