Abstract
Cytochrome P4501A (the CYP1A1 and CYP1A2 enzymes) are regulated through the aryl hydrocarbon receptor (AhR)-dependent signal transduction pathway and are generally known as enzymes which metabolize anthropogenic xenobiotics such as dioxin to carcinogenic and mutagenic compounds. However, recently the facts of CYP1A activation under physiological conditions or under action of non-dioxin-like compounds appear. In the present study we show that genistein, herbimycin A and geldanamycin (the protein-tyrosine kinase inhibitors) affect in vivo to CYP1A1 activity, the CYP1A1 mRNA level and the CYP1A1 protein level. These data provide insight into the role of protein kinases in CYP1A regulation may facilitate the understanding of CYP1A regulation.
Highlights
Cytochromes P450 are a superfamily of enzymes that play a critical role in the oxidizing metabolism of a wide range of endogenous and exogenous compounds
The CYP1A1 mRNA level, too, was increased by these three Protein-tyrosine kinases (PTKs) inhibitors (Figure 1(b)), that induced by herbimycin A (2-fold) being somewhat higher than that induced by geldanamycin (1.4-fold)
Western blot analysis was used to determine whether PTK inhibitors are capable of affecting the CYP1A1/2 protein level
Summary
Cytochromes P450 are a superfamily of enzymes that play a critical role in the oxidizing metabolism of a wide range of endogenous and exogenous compounds. Cytochromes P4501A1 (СYP1A1) and 1A2 (СYP1A2) metabolize planar hydrophobic substances such as polycyclic aromatic hydrocarbons and aromatic amines, forming cytotoxic and/or mutagenic products. It was thought that CYP1A can only be induced by compounds that are polycyclic and planar in structure; recent data have shown that compounds that have different chemical structures can do as much. The mechanisms of “non-classic” CYP1A activation are not yet clear [1]. AhR mediates a spectrum of toxic and carcinogenic effects of polycyclic aromatic hydrocarbons (PAHs) and arylamines by transcriptional activating CYP1A, a subfamily of the cytochrome P450 superfamily [2]
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