Cytochrome P450 (
P450)
enzymes and
ATP-binding cassette (ABC) transporters modulate the transport and
metabolism of both endogenous and exogenous
substrates and could play crucial roles in
the human brain. In this study, we report the transcript expression profile of seven
ABC transporters (
ABCB1, ABCC1-C5, and
ABCG2), 24
P450s (CYP1, CYP2, and CYP3 families and
CYP46A1), and 14 related
transcription factors [
aryl hydrocarbon receptor,
nuclear receptor (NR)1I2/
pregnane X receptor,
NR1I3/
constitutive androstane receptor and NR1C/
peroxisome proliferator-activated receptor, NR1H/
liver X receptor,
NR2B/
retinoid X receptor, and
NR3A/
estrogen receptor subfamilies] in the whole
brain, the
dura mater, and 17 different encephalic areas. In addition,
Western blotting and
immunohistochemistry analysis were used to characterize the distribution of the
P450s at the cellular and
subcellular levels in some
brain regions. Our results show the presence of a large variety of
xenobiotic transporters and
metabolizing enzymes in
human brain and show for the first time their apparent
selective distribution in different cerebral regions. The most abundant transporters were
ABCC5 and
ABCG2, which, interestingly, had a higher
mRNA expression in
the brain compared with that found in the
liver.
CYP46A1,
CYP2J2, CYP2U1,
CYP1B1,
CYP2E1, and
CYP2D6 represented more than 90% of the total
P450 and showed
selective distribution in different
brain regions. Their presence in both
microsomal and
mitochondrial fractions was shown both in
neuronal and
glial cells in several
brain areas. Thus, our study shows key
enzymes of
cholesterol and
fatty acid metabolism to be present in
the human brain and provides novel information of importance for elucidation of
enzymes responsible for normal and
pathological processes in
the human brain.
