To explore the effects of oxidative stress on metabolizing enzymes in blood cells, we examined the effect of hydrogen peroxide (H2O2) on glutathione S-transferase (GST) and cytochrome P450 (CYP) expression in a human erythroleukemic cell line, K562. After adding H2O2 (up to 100 μM) to the culture medium of K562 cells, the expression levels of GST and CYP enzymes were monitored by RT-PCR. The expression of GSTP1 and CYP3A4 was induced by oxidative stress. Quantitative PCR and immunoblot analysis revealed a 3- to 4-fold increase in GSTP1 and CYP3A4 mRNA, and a 2- to 3-fold increase in GSTP1 and CYP3A4 protein levels, 3 d after the addition of 100 μM H2O2. Induction was H2O2 dose-dependent and also depended on the length of culture. Our results suggest that oxidative stress may affect GST and/or CYP expression in human blood cells, which may alter the metabolism of drugs and xenobiotics and thus, the toxicity of these compounds to the blood cells.
ASJC Scopus subject areas
- Pharmaceutical Science