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Taurocholate transport by hepatic and intestinal bile acid transporters is independent of FIC1 overexpression in Madin-Darby canine kidney cells.
[benign recurrent intrahepatic cholestasis]
Mutations
in
the
human
familial
intrahepatic
cholestasis
gene
,
FIC
1
,
result
in
progressive
familial
intrahepatic
cholestasis
type
1
in
children
and
benign
recurrent
intrahepatic
cholestasis
.
The
present
study
was
performed
to
determine
whether
FIC
1
transports
bile
acids
and
/
or
influences
the
activity
of
apical
bile
acid
transporters
.
The
apical
secretion
assay
utilized
transfected
Madin-
Darby
canine
kidney
(
MDCK
)
cells
,
which
stably
express
the
bile
acid
uptake
protein
,
Na
+
/
taurocholate
co
-transporting
polypeptide
(
NTCP
)
.
These
cells
were
then
transiently
transfected
with
FIC
1
and
/
or
the
bile
salt
export
pump
(
BSEP
)
and
were
grown
on
Transwell
filters
to
form
a
polarized
monolayer
.
[
(
3
)
H
]
Taurocholate
was
added
to
the
basal
medium
and
the
taurocholate
secretion
was
measured
in
the
apical
medium
.
A
second
assay
,
apical
uptake
assays
,
utilized
polarized
MDCK-
II
cells
,
which
were
transiently
transfected
with
FIC
1
,
FIC
1
mutants
and
/
or
the
apical
sodium-dependent
bile
acid
transporter
(
ASBT
)
.
[
(
3
)
H
]
Taurocholate
was
added
to
the
apical
media
and
intracellular
uptake
of
taurocholate
was
measured
.
Apical
secretion
assays
:
FIC
1
expression
in
MDCK
/
NTCP
cells
had
no
effect
on
taurocholate
secretion
compared
to
controls
.
In
contrast
,
apical
secretion
of
taurocholate
in
BSEP-transfected
cells
was
approximately
twofold
higher
than
in
non-transfected
MDCK
/
NTCP
cells
(
P
<
0
.
01
)
.
The
BSEP-mediated
secretion
was
unaffected
by
co
-transfection
with
FIC
1
.
Apical
uptake
assays
:
taurocholate
uptake
in
ASBT
expressing
cells
was
6
.
5
-
fold
higher
than
in
controls
and
was
unaffected
by
co
-transfection
of
cells
with
FIC
1
or
FIC
1
mutants
.
These
results
indicate
that
FIC
1
does
not
transport
taurocholate
and
,
when
overexpressed
in
MDCK
cells
,
had
no
effect
on
the
function
of
BSEP
or
ABST
.
Diseases
Validation
Diseases presenting
"the taurocholate secretion was measured in the apical medium"
symptom
benign recurrent intrahepatic cholestasis
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