TY - JOUR
T1 - Disruption of c-Fos leads to increased expression of NAD(P)H:quinone oxidoreductase1 and glutathione S-transferase
AU - Wilkinson IV, John
AU - Radjendirane, Venugopal
AU - Pfeiffer, Gordon R.
AU - Jaiswal, Anil K.
AU - Clapper, Margie L.
N1 - Funding Information:
This work was supported by NIH grants GM47466 (to A.K.J.) and CA64726 (to M.L.C.).
PY - 1998/12/30
Y1 - 1998/12/30
N2 - Regulation of the basal and induced expression of detoxifying enzymes such as NAD(P)H:quinone oxidoreductase1 (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 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.
AB - Regulation of the basal and induced expression of detoxifying enzymes such as NAD(P)H:quinone oxidoreductase1 (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 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.
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U2 - 10.1006/bbrc.1998.9804
DO - 10.1006/bbrc.1998.9804
M3 - Article
C2 - 9918819
AN - SCOPUS:0032583548
SN - 0006-291X
VL - 253
SP - 855
EP - 858
JO - Biochemical and biophysical research communications
JF - Biochemical and biophysical research communications
IS - 3
ER -