Astaxanthin rich crude extract of Haematococcus pluvialis induces cytochrome P450 1A1 mRNA by activating aryl hydrocarbon receptor in rat hepatoma H4IIE cells

The xanthophyll, astaxanthin (Ax), strongly induces cytochrome P450 (CYP) 1A-dependent activity in rats and mice, via increased transcription of Cyp1a1 mRNA through an undetermined mechanism. In this study, we have investigated how aryl hydrocarbon receptor (AhR)-related events are affected by the addition of Ax-rich crude extract from Haematococcus pluvialis in H4IIE rat hepatoma cells. The expression of Cyp1a1 mRNA was significantly increased by exposure to H. pluvialis extract (100 μmol/l, 17.6-fold). The highest level of Cyp1a1 mRNA was observed after a 6-h exposure to H. pluvialis extract (25-fold), but 12- and 24-h exposures resulted in lower levels of induction. Green fluorescence protein-tagged AhR was translocated into the nucleus in COS-7 cells after a 10 min exposure to Ax. Moreover, H. pluvialis extract containing Ax activated the human CYP1A1 enhancer region in a luciferase assay, and a gel shift assay showed that nuclear proteins stimulated by H. pluvialis extract can interact specifically with xenobiotic responsive elements (XREs) in the CYP1A1 promoter. Together these results indicate the possibility that Ax, contained in H. pluvialis extract, caused the induction of Cyp1a1 mRNA through the activation and translocation of an XRE-binding form of AhR.