In a recent report, peroxisome proliferator-activated receptor (
PPAR)-gamma/RXR-a heterodimers were shown to regulate
BCO gene expression, and 9-
cis-retinoic acid treatment induced the expression in mice.
33 In our study, neither 9-
cis-retinoic acid nor 9-
cis-β-carotene was detected in the cells after β-carotene incubation. Therefore, a role of 9-
cis-retinoic acid in the observed effects on the regulation of
BCO expression in D407 cells can most probably be excluded. We also performed a transcription factor binding site search in the 5′ flanking region of the human
BCO gene (GenBank sequence database) that revealed a putative RARE (GGGTCActtgAGGTCA, 600 bases upstream to the start site; Chichili GR, unpublished observation, 2004). Therefore, we assume that
RAR-a and
RXR-a are involved in the regulation of
BCO expression in D407 cells and thus most probably are also involved in vivo in the RPE. Bachman et al.,
34 demonstrated in rats and chicken that retinoic acid feeding results in a decrease in BCO enzyme activity in intestines but did not affect
BCO activity in liver. Our data partially agree with the observation that high RA concentrations inhibit
BCO expression. However, we also found that low RA levels have a positive effect on
BCO mRNA expression. The fact that RA induces
BCO expression at a lower concentration may contribute to efficient the use of β-carotene for retinoid synthesis, whereas the suppression of
BCO expression at higher RA concentration may avoid an excess of retinoid synthesis from its provitamin A precursor. Further investigations are necessary to gain a mechanistic understanding of the regulation of
BCO expression via RA and its nuclear receptors in different cell types and organisms.