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J Biol Chem, Vol. 274, Issue 47, 33398-33402, November 19, 1999
From the The clearance of free cholesterol from plasma
lipoproteins by tissues is of major quantitative importance, but it is
not known whether this is passive or receptor-mediated. Based on our
finding that scavenger receptor BI (SR-BI) promotes free cholesterol
(FC) exchange between high density lipoprotein (HDL) and cells, we tested whether SR-BI would effect FC movement in vivo using
[14C]FC- and [3H]cholesteryl ester
(CE)-labeled HDL in mice with increased (SR-BI transgenic (Tg)) or
decreased (SR-BI attenuated (att)) hepatic SR-BI expression. The
initial clearance of HDL FC was increased in SR-BI Tg mice by 72% and
decreased in SR-BI att mice by 53%, but was unchanged in apoA-I
knockout mice compared with wild-type mice. Transfer of FC to non-HDL
and esterification of FC were minor and could not explain differences.
The hepatic uptake of FC was increased in SR-BI Tg mice by 34% and
decreased in SR-BI att mice by 22%. CE clearance and uptake gave
similar results, but with much slower rates. The uptake of HDL FC and
CE by SR-BI Tg primary hepatocytes was increased by 2.2- and 2.6-fold
(1-h incubation), respectively, compared with control hepatocytes. In
SR-BI Tg mice, the initial biliary secretion of [14C]FC
was markedly increased, whereas increased [3H]FC appeared
after a slight delay. Thus, in the mouse, a major portion of the
clearance of HDL FC from plasma is mediated by SR-BI.
Plasma high density lipoprotein
(HDL)1 plays a key role in
maintaining cholesterol homeostasis. Epidemiological studies
demonstrated a strong inverse correlation between HDL levels and the
risk of coronary artery disease (1). Although detailed mechanisms
remain uncertain, it has been proposed that HDL promotes reverse
cholesterol transport by facilitating transfer of cholesterol from
peripheral tissues to the liver for secretion into bile (Ref. 2; see
Ref. 3 for a recent review). Early studies using HDL and low density lipoprotein (LDL) with radiolabeled free cholesterol (FC) showed that
FC in HDL is the preferred source for biliary cholesterol (4-8).
Recent work with plant sterols provided further evidence that HDL is
the preferred carrier for the transport of cholesterol into bile (9).
Based on the observations that HDL FC is preferentially utilized for
biliary secretion and that, in tissue culture studies, HDL, but not
LDL, selectively binds FC (10), Schwartz et al. (5)
predicted that a cell-surface HDL receptor might be involved in the
hepatic uptake of HDL FC. As a counterpoint to this idea, free
cholesterol exchanges readily between lipoproteins and cells, suggesting that passive FC uptake by the liver might be possible.
Scavenger receptor BI (SR-BI) has recently been identified as an
authentic HDL receptor that mediates the selective uptake of HDL
cholesteryl ester (CE) (11) and bi-directional transfer of FC between
HDL and cells (12, 13). Its tissue distribution (11, 14) and
regulatable expression in the adrenal gland, testis, and ovary (14, 15)
indicate that the receptor plays an important physiological role in
cholesterol metabolism (16, 17). Hepatic overexpression of SR-BI leads
to decreased HDL levels in mice (18-20) due to accelerated hepatic
uptake of HDL CE and subsequently increased HDL CE and protein
catabolism (19). On the other hand, decreased expression of SR-BI in
gene-targeted mice results in increased HDL levels (21, 22).
Furthermore, SR-BI mRNA is expressed in thickened intima of
atheromatous aorta (12), and the receptor suppresses the development of
atherosclerosis in SR-BI transgenic (SR-BI Tg)/LDL receptor-deficient
compound mice fed the Paigen diet (23).
In our previous work, we found that, in transfected Chinese hamster
ovary cells, SR-BI mediates the cellular uptake of HDL FC as well as CE
(12). Moreover, SR-BI promotes cholesterol efflux from cells to HDL
(12, 13) or protein-free phospholipid (PL) vesicles (13), and the
efflux rates correlate with the expression level of SR-BI in different
cell lines (Refs. 12 and 13; see Ref. 24 for review). In mice with
hepatic overexpression of SR-BI, the biliary concentration of
cholesterol is increased (18, 25). These results led us to hypothesize
that SR-BI plays a physiological role in vivo in promoting
the hepatic uptake of HDL FC and facilitating the secretion of
cholesterol into bile. We tested this hypothesis in mice with increased
or attenuated expression of SR-BI.
Animals--
SR-BI Tg and SR-BI att mice were generated as
described previously (19, 22). ApoA-I knockout (apoA-I0) mice were
purchased from Jackson Laboratory. The SR-BI Tg mice used have been
backcrossed with C57BL/6J mice five times, and the apoA-I knockout mice
backcrossed with C57BL/6J mice >10 times. The SR-BI att mice were in a
mixed background of BALB/c/ByJ and C57BL/6J (22). The animals were 6 months old, weighed 25-35 g, and were housed at 22 °C under a
constant light/dark cycle (7:00 a.m. to 7:00 p.m.) with ad
libitum access to water and rodent chow. Before the experiments,
animals were fasted for 10-12 h (11:00 p.m. to 9:00-11:00 a.m.).
Clearance of HDL Cholesterol--
HDL (d = 1.063-1.21) was provided from human plasma by sequential
ultracentrifugation and was dual-labeled with [4-14C]FC
and [cholesteryl-1,2,6,7-3H]cholesteryl oleate
(NEN Life Science Products) or labeled with [cholesteryl-1,2-3H]cholesteryl oleoyl ether
(CEth) (Amersham Pharmacia Biotech) (26). The specific radioactivity of
the dual-labeled HDL was ~55,000 cpm [14C]FC/µg of
HDL FC and 36,000 cpm [3H]CE/µg of HDL CE. Animals were
lightly anesthetized and injected with dual-labeled HDL in 0.1 ml of
phosphate-buffered saline via the femoral vein. Blood was collected
periodically via the retro-orbital plexus; the plasma was immediately
separated; and the HDL fraction was rapidly obtained by precipitating
LDL and very low density lipoprotein with heparin/Mn2+ (HDL
cholesterol reagent, Sigma). The radioactivity in HDL and the plasma
was determined with a
To measure esterification of HDL FC in the plasma, plasma samples were
collected periodically and lipid-extracted (28); FC and CE were
separated by TLC; and radioactivity was measured. The esterification
ratio is expressed as the percentage of cholesterol converted to ester.
Uptake of HDL Cholesterol by Liver and Hepatocytes--
At the
end of clearance experiments (usually 1 h post-injection), the
liver was perfused thoroughly via the portal vein with phosphate-buffered saline. The liver was blotted dry, weighed, and
stored at
Primary hepatocytes were isolated by a two-step collagenase perfusion
(collagenase type I (Worthington), ~0.3 mg/ml in Hanks' balanced
solution supplemented with 10 mM Hepes, pH 7.4) (30). To
prevent nonspecific digestion, protease inhibitors
(CompleteTM, EDTA-free tablets, Roche Molecular
Biochemicals) were added to the perfusion buffer according to the
manufacturer's instruction. Viable cells were obtained after low speed
centrifugation in Percoll (Sigma). The cells were then washed,
resuspended, and maintained on a six-well plate in Williams' E medium
supplemented with 7% fetal bovine serum, insulin/transferrin/sodium
selenite (Life Technologies, Inc.), 30 mM pyruvate, and
penicillin/streptomycin at 37 °C under 5% CO2. The HDL
cholesterol uptake experiment was performed the next day with 0.5%
bovine serum albumin in Williams' E medium. After incubation with
dual-labeled HDL, cells were washed, and the cell-associated
radioactivity was measured (12).
Biliary Secretion of HDL Cholesterol--
The animals were
anesthetized with ketamine (140 µg/g) and xylazine (14 µg/g)
intraperitoneally. The abdomen was opened; the distal part of the
common bile duct was ligated; and the gallbladder was incised and
cannulated. The dual- or [3H]CEth-labeled HDL was
injected, and bile samples were collected periodically while the
animals were placed under a heating lamp to maintain body temperature.
The radioactivity in bile was determined by either direct counting (no
more than 40 µl of bile in 10 ml of scintillation mixture) or
counting after lipid extraction and TLC.
Statistical Analysis--
Statistical analysis was performed by
two-tailed Student's t test for unpaired data.
Effect of SR-BI on Clearance of HDL FC in Plasma--
To explore
the role of SR-BI in the metabolism of HDL FC, the clearance of HDL
cholesterol was studied in mice with different levels of hepatic SR-BI
expression. [14C]FC- and [3H]CE-labeled HDL
was injected intravenously, and blood samples were obtained at
different time points. To avoid ex vivo transfer of free
cholesterol radioactivity between lipoproteins, HDL was rapidly
separated from other plasma components by precipitation (7, 31). As
shown in Fig. 1A, the
clearance of HDL [14C]FC was dramatically faster in SR-BI
Tg mice and slower in SR-BI att mice. Fifty percent of HDL FC was
removed from the plasma within 1.8 min (t1/2) in
SR-BI Tg mice, compared with 3.2 and 7.0 min in WT and SR-BI att mice, respectively. To determine whether the increased clearance of HDL FC in
SR-BI Tg mice was due simply to a decreased level of HDL, the clearance
of HDL FC was also measured in apoA-I0 mice, which have similarly
decreased levels of HDL (32), but normal hepatic SR-BI expression (14).
Despite dramatically decreased plasma HDL levels, apoA-I0 mice
exhibited a similar clearance of HDL FC compared with WT mice,
especially in the initial stage (t1/2 = 3.0 min)
(Fig. 1A).
To determine whether the accelerated clearance of HDL FC in SR-BI
Tg mice was caused by rapid transfer of HDL FC to other plasma
lipoproteins, the clearance of [14C]FC in the non-HDL
fraction of the plasma was measured. As shown in Fig. 1B,
the activity of [14C]FC in the non-HDL fraction was
relatively low and similar in mice of different genotypes, indicating
that transfer of HDL [14C]FC to non-HDL lipoproteins
could not account for differences in the rapid disappearance of HDL
[14C]FC.
The FCRs of HDL FC in different mice were calculated using a
two-compartment model (27) and are shown in Table
I. The FCR was increased by 292% in
SR-BI Tg mice and decreased by 54% in SR-BI att mice compared with WT
mice (p < 0.01 for both). The FCR was increased by
66% in apoA-I0 mice (p < 0.01) compared with WT mice,
reflecting the strong influence of the final time point in the model.
However, when the initial rate of clearance was calculated, the value
was almost the same for apoA-I0 and WT mice (15.8 versus
16.3 pools/h), but the increase in SR-BI Tg mice and the decrease in
SR-BI att mice remained (by 72 and 53%; p = 0.007 and
0.00001, respectively) (Table I). The data indicate that the observed
differences in HDL FC clearance are related primarily to SR-BI
expression and not to HDL pool size.
To assess the possibility of HDL cholesterol being rapidly taken up by
the liver as ester, the esterification rate of HDL FC in plasma was
measured. The esterification of FC was negligible 0.5 min after HDL
injection: 0.6 and 0.4% of HDL [14C]FC was esterified in
WT and SR-BI Tg mice, respectively. At 4 min, only 2.1 and 1.6% of
[14C]FC was converted to ester, whereas by that time,
>60 and 80% of [14C]FC had already been removed from
HDL in WT and SR-BI Tg mice, respectively (Fig. 1A).
Cholesterol esterification is decreased in SR-BI Tg mice due to a
functional deficiency of lecithin:cholesterol acyltransferase (19).
Therefore, the rapid clearance of HDL [14C]FC in SR-BI Tg
mice was not a result of the hepatic uptake of esterified
[14C]cholesterol from HDL.
The clearance of HDL CE was measured simultaneously with the clearance
of HDL FC (data not shown). Consistent with our earlier observations
(19, 22), the clearance of HDL [3H]CE was accelerated in
SR-BI Tg mice (t1/2 = 0.4 h) and decreased in
SR-BI att mice (t1/2 = 2.4 h) compared with WT
mice (t1/2 = 1.1 h); the clearance of HDL
[3H]CE in apoA-I0 mice (t1/2 = 0.9 h) was similar to that in WT mice. In all cases, HDL CE was
cleared much slower than HDL FC.
Effect of SR-BI on Hepatic Uptake of HDL FC--
SR-BI Tg mice
overexpress SR-BI specifically in the liver, whereas SR-BI att mice
have 50% decreased hepatic expression of SR-BI. To determine the
effect of SR-BI expression on the hepatic uptake of HDL
[14C]FC from the plasma, the accumulation of
[14C]FC in the liver was measured. As shown in Fig.
2, ~76% of [14C]FC was
taken up by the liver in SR-BI Tg mice 1 h after HDL was injected,
a 34% increase compared with WT mice (p < 0.05). In
contrast, SR-BI att mice exhibited a 22% decrease in the hepatic uptake of HDL FC (p < 0.05). Compared with WT mice,
the uptake of HDL [14C]FC by the liver in apoA-I0 mice
was not significantly different (47% versus 42%).
Similarly, the hepatic uptake of HDL [3H]CE was increased
by 346% in SR-BI Tg mice and decreased by 63% in SR-BI att mice
(p < 0.01 for both), consistent with earlier reports
(19, 22). The uptake of HDL CE in apoA-I0 mice was not significantly
different from that in WT mice (10.3% versus 9.4%).
In vitro experiments were also performed to compare the
uptake of HDL cholesterol by primary hepatocytes with different
expression levels of SR-BI. The SR-BI protein levels in primary
hepatocytes from SR-BI Tg mice, assessed at the end of the experiments,
were ~6-fold higher than in hepatocytes from control mice (data not shown). During a 1-h incubation, hepatocytes in primary culture from
SR-BI Tg mice exhibited a 2.2-fold increase in the uptake of HDL
[14C]FC compared with WT hepatocytes; the uptake of HDL
[3H]CE was increased by 2.6-fold in SR-BI Tg hepatocytes
(Fig. 3). Thus, the cellular uptake of
HDL FC and CE by hepatocytes was stimulated by increased levels of
SR-BI expression. Taken together, both in vivo and in
vitro data demonstrate clearly that SR-BI plays a critical role in
the hepatic uptake of HDL FC as well as HDL CE from the
circulation.
Effect of SR-BI on Biliary Cholesterol Secretion--
To explore
the role of SR-BI in biliary cholesterol secretion, dual-labeled HDL
was injected, and the transport of HDL cholesterol into bile was
compared in different mice. The rise in biliary [14C]FC
radioactivity paralleled the fall in plasma HDL [14C]FC
radioactivity and reached a plateau within 17.5 min (Fig. 4A). As shown in Fig. 4, in
SR-BI Tg mice, HDL [14C]FC radioactivity appeared more
rapidly in bile than HDL [3H]CE radioactivity. At 2.5 and
7.5 min, the secretion of HDL [14C]FC into bile was
increased by 5.1- and 1.6-fold, respectively, compared with WT mice
(p < 0.05 for both). In contrast, the initial secretion rate of cholesterol derived from HDL [3H]CE was
not significantly different in SR-BI Tg mice versus WT mice,
but was significantly increased at later time points (Fig. 4B). SR-BI att mice tended to have decreased biliary
secretion of HDL FC and CE radioactivity, although the difference
between SR-BI att and WT mice was not significant (Fig. 4).
Nevertheless, these data indicate that SR-BI overexpression enhances
the rate of biliary secretion of cholesterol derived from both HDL FC
and CE.
Biliary cholesterol from SR-BI Tg mice was characterized by TLC after
lipid extraction. Although almost all (>99%) HDL
[14C]FC remained unesterified in bile, ~73% of HDL
[3H]CE appeared in unesterified form, and surprisingly,
27% was secreted into bile as CE. To confirm this observation, HDL
labeled with non-hydrolyzable [3H]CEth was injected. A
portion of [3H]CEth (0.2%) was detected in bile 1 h
after HDL injection, compared with 2.1% of HDL [3H]CE
and 2.2% of HDL [14C]FC. The results indicate that, in
mice, a significant amount of HDL CE is secreted into bile as an intact
molecule, although most of HDL CE is hydrolyzed before secretion.
This study provides the first evidence for an in vivo
role of SR-BI in the metabolism of HDL FC. SR-BI promotes the uptake of
HDL FC by primary hepatocytes and facilitates the rapid clearance of
HDL FC by the liver. The magnitude of these effects was large (Fig. 1
and Table I), suggesting that a major part of the clearance of FC from
plasma is receptor-mediated rather than passive. Furthermore, SR-BI
overexpression enhances the secretion of HDL cholesterol radioactivity
into bile, including both the initial secretion of HDL FC and the
slower secretion of FC and CE derived from HDL CE. Our study provides
strong evidence that the rapid clearance of HDL FC by the liver and its
subsequent appearance in bile (5) can be mediated by SR-BI.
HDL plays a central role in cholesterol homeostasis. It has been
recognized for >2 decades that HDL FC is the preferred substrate for
biliary steroid (see Ref. 33 for review). Schwartz et al. (4, 34) first demonstrated that the cholesterol used for biliary
steroid secretion is derived substantially from plasma lipoprotein FC
rather than CE. By injecting [3H]FC- or
[14C]FC-labeled HDL and LDL simultaneously into bile
fistula patients, these investigators further showed that a much larger
fraction of HDL FC than LDL FC is used for biliary secretion and that
the radioactivity of HDL FC appears and peaks in bile much faster than
that of LDL (5, 6). Similar results were obtained in squirrel monkeys
(7) and rats (8, 35). However, the molecular basis for this preference
of HDL FC was not clear. We now provide evidence that a cell-surface
HDL receptor is involved. SR-BI has high affinity for HDL (11) and
greatly accelerates the transport of HDL FC across the liver into bile
(Figs. 1A and 4A). SR-BI also binds to LDL and
possibly other lipoproteins, but with a lower affinity (36), which may
account for the less favorable utilization of FC from other
lipoproteins for biliary secretion (33). Although only 4-5% of HDL
cholesterol (FC + CE) radioactivity appeared in bile, based on the
relatively large HDL cholesterol pool size and assuming a similar
specific activity of HDL and the liver cholesterol pool that acts as a
precursor of biliary cholesterol, this could be enough to explain the
output of biliary cholesterol in SR-BI Tg mice, which is increased by
50%. Several studies suggested that, in rats (52) and primates (34,
53, 54), HDL CE makes a minor contribution to the precursor pool of
biliary cholesterol. Results from our study indicate that, at least in
mice, cholesterol derived from HDL CE can be secreted into bile after
hydrolysis and make a contribution equivalent to that of FC.
Furthermore, HDL CE can also be delivered to bile in the intact form,
although, in the human, almost all biliary cholesterol exists as FC
(55).
The mechanism by which SR-BI mediates the uptake of FC or CE by cells
is poorly understood. The mere tethering of HDL or an acceptor to the
plasma membrane by SR-BI is essential but probably not sufficient to
produce maximal cholesterol transfer between the two surfaces.
Comparative studies indicated that other class B scavenger receptors
such as CD36 and a splicing variant of SR-BI (SR-BII) bind HDL with
similar affinity, but facilitate FC efflux as well as selective lipid
uptake to a much reduced extent (43-46). In contrast, various PL
vesicles with a wide range of affinities for SR-BI promote cholesterol
efflux to a remarkably similar extent (43). On the other hand, the
efflux rates of FC to HDL or PL vesicles correlate strongly with the
levels of SR-BI expression in several different cell lines (12, 13),
indicating that the highly efficient promotion of cholesterol transfer
between HDL and the cell plasma membrane is a unique property of SR-BI. Structural and functional studies from several laboratories suggest that the extracellular domain of SR-BI is critical for efficient lipid
transfer (45, 46), although the C-terminal cytoplasmic domain may also
play an important role (46). Although the exact roles the domains play
remain unclear, Rothblat and co-workers (24, 43) observed recently that
SR-BI increases the susceptibility of plasma membrane cholesterol to
cholesterol oxidase and changes the kinetics of cholesterol efflux to
cyclodextrins. It was further proposed that SR-BI may induce
redistribution of cholesterol in the plasma membrane and create
microdomains with different degrees of cholesterol enrichment that
favor transfer of cholesterol from/to the membrane (24, 43). Caveolae
may be one of these candidate cholesterol-rich membrane domains since
they are involved in intracellular cholesterol trafficking (47) and
also mediate cholesterol efflux (48, 49). SR-BI has been shown to be
palmitoylated (50) and to colocalize with caveolae (44, 50). Recently,
Graf et al. (51) demonstrated that, during selective uptake,
HDL CEth is initially transferred to caveolae and that the transfer
requires SR-BI. The initial step of HDL FC transfer into bile could
involve transfer of HDL FC into caveolae.
SR-BI enhances the exchange of cholesterol between the surface of HDL
and the cell. The direction of net flux will largely depend on the
chemical gradient between the two surfaces. SR-BI may be expressed at
both sinusoidal and canalicular membranes of hepatocytes (18). On the
sinusoidal side of hepatocytes, SR-BI facilitates the net transfer of
FC from HDL to the plasma membrane, whereas on the canalicular side,
SR-BI might promote the release of FC from the membrane to such
acceptors as PL vesicles. The excretion of HDL cholesterol into bile is
thought to be facilitated by the biliary secretion of PL at the
canalicular membrane (39), a process now known to be mediated by a PL
translocase, the ATP-dependent Mdr2 P-glycoprotein (40).
Also the secretion of HDL FC into bile can be stimulated by the luminal
bile salt-mediated solubilization of cholesterol independent of PL
secretion (41). The secretion of bile salts at the canalicular membrane
was recently shown to be mediated mainly by another member of the
ATP-binding cassette transporter superfamily, the sister of
P-glycoprotein (42). Hepatic overexpression of SR-BI causes increased
biliary secretion of cholesterol without a concomitant increase in PL
or bile salt secretion (18, 25). Based on the evidence available, a
working model would be that, through an energy-dependent
process, a membrane transporter at the canalicular membrane (a PL
flippase or a bile salt export pump) generates a FC chemical gradient
from blood to bile; SR-BI may promote the transport of HDL cholesterol
along this gradient at the sinusoidal and/or canalicular membrane by binding HDL or a cholesterol acceptor to the membrane.
This study has provided further evidence for a major role of SR-BI in
reverse cholesterol transport. HDL is the preferred acceptor of
cholesterol from peripheral tissues (31, 37). Our earlier work
demonstrated that SR-BI mediates HDL-dependent cellular
cholesterol efflux and may facilitate cholesterol efflux in the
arterial wall (12, 13). The current results indicate that SR-BI also
stimulates the hepatic uptake of HDL FC and its transport into bile. It
is possible that SR-BI catalyzes free cholesterol transfer down a
gradient resulting from bile formation. SR-BI may promote reverse
cholesterol transport by facilitating both the initial and final steps
in the process.
We thank X. C. Jiang, C. Welch, L. M. Varban, T. Arai, D. L. Silver, C. P. Liang, and M. D. Shindler for expert advice and assistance.
*
This work was supported by National Institutes of Health
Grants HL58033 and HL54591 and in part by a grant from Eli Lilly Inc.The costs of publication of this
article were defrayed in part by the
payment of page charges. The article
must therefore be hereby marked
"advertisement" in
accordance with 18 U.S.C. Section
1734 solely to indicate this fact.
**
To whom correspondence should be addressed: Dept. of Medicine,
Columbia University, 630 W. 168th St., New York, NY 10032. Tel.:
212-305-4899; Fax: 212-305-6052.
The abbreviations used are:
HDL, high density
lipoprotein;
LDL, low density lipoprotein;
FC, free cholesterol;
SR-BI, scavenger receptor BI;
Tg, transgenic;
att, attenuated;
CE, cholesteryl
ester;
PL, phospholipid;
CEth, cholesteryl oleoyl ether;
FCR, fractional clearance rate;
WT, wild-type.
Hepatic Scavenger Receptor BI Promotes Rapid Clearance of High
Density Lipoprotein Free Cholesterol and Its Transport into Bile*
,,
,**
Division of Molecular Medicine, Millennium Pharmaceuticals, Inc.,
Cambridge, Massachusetts 02139
ABSTRACT
TOP
ABSTRACT
INTRODUCTION
MATERIALS AND METHODS
RESULTS
DISCUSSION
REFERENCES
INTRODUCTION
TOP
ABSTRACT
INTRODUCTION
MATERIALS AND METHODS
RESULTS
DISCUSSION
REFERENCES
MATERIALS AND METHODS
TOP
ABSTRACT
INTRODUCTION
MATERIALS AND METHODS
RESULTS
DISCUSSION
REFERENCES
-counter. The radioactivity in the non-HDL
fraction was obtained by subtracting the radioactivity in HDL from that
in the plasma. The radioactivity of 0.5 min post-injection is defined
as 100% of injected radioactivity. Based on the clearance curves of
HDL tracers (see Fig. 1A), fractional clearance rates (FCRs)
were calculated using a two-compartment model as described (27).
80 °C. A 200-mg piece was later homogenized and lipid-extracted (29), and radioactivity was determined. The total
accumulation of HDL [14C]FC in the liver of each
individual mouse was calculated from the total weight of the organ.
RESULTS
TOP
ABSTRACT
INTRODUCTION
MATERIALS AND METHODS
RESULTS
DISCUSSION
REFERENCES
View larger version (20K):
[in a new window]
Fig. 1.
Kinetics of clearance of HDL
[14C]FC in plasma. HDL [14C]FC was
injected intravenously into female mice; plasma and HDL samples were
obtained immediately; and the radioactivity remaining in the plasma or
HDL (means ± S.D., n = 5) was determined.
A, clearance of [14C]FC in HDL. The
radioactivity in HDL 0.5 min post-injection is defined as 100%.
B, clearance of [14C]FC in non-HDL
lipoproteins. The values were obtained by subtracting the radioactivity
in HDL from that in the plasma. The radioactivity in the plasma 0.5 min
post-injection is defined as 100%.
Fractional clearance rates of HDL [14C]FC and
[3H]CE in mice
View larger version (16K):
[in a new window]
Fig. 2.
Uptake of HDL [14C]FC by
liver. One hour after HDL [14C]FC was injected into
mice, the liver was perfused thoroughly and stored at 80 °C. A
200-mg piece was later homogenized and lipid-extracted, and
radioactivity was determined. The values (means ± S.D.,
n = 5) are the radioactivity accumulated in the liver
expressed as the percentage of the total HDL [14C]FC
injected. *, p < 0.05 as compared with WT mice.
View larger version (13K):
[in a new window]
Fig. 3.
Uptake of HDL [14C]FC by
hepatocytes. Primary hepatocytes were obtained from wild-type or
SR-BI Tg mice by collagenase perfusion as described under "Materials
and Methods." Cells were incubated with HDL (2.2 µg of CE/ml)
labeled with [14C]FC and [3H]CE for 1 h at 37 °C, and cell-associated radioactivity was measured. Values
are means ± S.D. (n = 3). cell. prot.,
cellular protein.
View larger version (17K):
[in a new window]
Fig. 4.
Kinetics of biliary secretion of HDL
[14C]FC (A) and [3H]CE
(B). Bile was collected as described under
"Materials and Methods," and the radioactivity in the bile was
measured. The values are plotted at the midpoint of each period during
which the bile samples were collected. Values are means ± S.D.
(n = 5). * and **, p < 0.05 and
p < 0.01, respectively, as compared with WT
mice.
DISCUSSION
TOP
ABSTRACT
INTRODUCTION
MATERIALS AND METHODS
RESULTS
DISCUSSION
REFERENCES
ACKNOWLEDGEMENTS
FOOTNOTES
ABBREVIATIONS
REFERENCES
TOP
ABSTRACT
INTRODUCTION
MATERIALS AND METHODS
RESULTS
DISCUSSION
REFERENCES
1.
Gordon, D. J.,
and Rifkind, B. M.
(1989)
N. Engl. J. Med.
321,
1311-1316[Medline]
[Order article via Infotrieve]
2.
Glomset, J. A.
(1968)
J. Lipid Res.
9,
155-167[Abstract]
3.
Tall, A. R.
(1998)
Eur. Heart J.
19 Suppl. A,
A31-35
4.
Schwartz, C. C.,
Berman, M.,
Vlahcevic, Z. R.,
Halloran, L. G.,
Gregory, D. H.,
and Swell, L.
(1978)
J. Clin. Invest.
61,
408-423
5.
Schwartz, C. C.,
Halloran, L. G.,
Vlahcevic, Z. R.,
Gregory, D. H.,
and Swell, L.
(1978)
Science
200,
62-64 6.
Halloran, L. G.,
Schwartz, C. C.,
Vlahcevic, Z. R.,
Nisman, R. M.,
and Swell, L.
(1978)
Surgery (St. Louis)
84,
1-7[Medline]
[Order article via Infotrieve]
7.
Portman, O. W.,
Alexander, M.,
and O'Malley, J. P.
(1980)
Biochim. Biophys. Acta
619,
545-558[Medline]
[Order article via Infotrieve]
8.
Bravo, E.,
Cantafora, A.,
and Argiolas, L.
(1989)
Biochim. Biophys. Acta
1003,
315-320[Medline]
[Order article via Infotrieve]
9.
Robins, S. J.,
and Fasulo, J. M.
(1997)
J. Clin. Invest.
99,
380-384[Medline]
[Order article via Infotrieve]
10.
Stein, Y.,
Glangeaud, M. C.,
Fainaru, M.,
and Stein, O.
(1975)
Biochim. Biophys. Acta
380,
106-118[Medline]
[Order article via Infotrieve]
11.
Acton, S.,
Rigotti, A.,
Landschulz, K. T.,
Xu, S.,
Hobbs, H. H.,
and Krieger, M.
(1996)
Science
271,
518-520[Abstract]
12.
Ji, Y.,
Jian, B.,
Wang, N.,
Sun, Y.,
Moya, M. L.,
Phillips, M. C.,
Rothblat, G. H.,
Swaney, J. B.,
and Tall, A. R.
(1997)
J. Biol. Chem.
272,
20982-20985 13.
Jian, B.,
de la Llera-Moya, M.,
Ji, Y.,
Wang, N.,
Phillips, M. C.,
Swaney, J. B.,
Tall, A. R.,
and Rothblat, G. H.
(1998)
J. Biol. Chem.
273,
5599-5606 14.
Wang, N.,
Weng, W.,
Breslow, J. L.,
and Tall, A. R.
(1996)
J. Biol. Chem.
271,
21001-21004 15.
Landschulz, K. T.,
Pathak, R. K.,
Rigotti, A.,
Krieger, M.,
and Hobbs, H. H.
(1996)
J. Clin. Invest.
98,
984-995[Medline]
[Order article via Infotrieve]
16.
Steinberg, D.
(1996)
Science
271,
460-461[CrossRef][Medline]
[Order article via Infotrieve]
17.
Fidge, N. H.
(1999)
J. Lipid Res.
40,
187-201 18.
Kozarsky, K. F.,
Donahee, M. H.,
Rigotti, A.,
Iqbal, S. N.,
Edelman, E. R.,
and Krieger, M.
(1997)
Nature
387,
414-417[CrossRef][Medline]
[Order article via Infotrieve]
19.
Wang, N.,
Arai, T.,
Ji, Y.,
Rinninger, F.,
and Tall, A. R.
(1998)
J. Biol. Chem.
273,
32920-32926 20.
Ueda, Y.,
Royer, L.,
Gong, E.,
Zhang, J.,
Cooper, P. N.,
Francone, O.,
and Rubin, E. M.
(1999)
J. Biol. Chem.
274,
7165-7171 21.
Rigotti, A.,
Trigatti, B. L.,
Penman, M.,
Rayburn, H.,
Herz, J.,
and Krieger, M.
(1997)
Proc. Natl. Acad. Sci. U. S. A.
94,
12610-12615 22.
Varban, M. L.,
Rinninger, F.,
Wang, N.,
Fairchild-Huntress, V.,
Dunmore, J. H.,
Fang, Q.,
Gosselin, M. L.,
Dixon, K. L.,
Deeds, J. D.,
Acton, S. L.,
Tall, A. R.,
and Huszar, D.
(1998)
Proc. Natl. Acad. Sci. U. S. A.
95,
4619-4624 23.
Arai, T.,
Wang, N.,
Bezouevski, M.,
Welch, C.,
and Tall, A. R.
(1999)
J. Biol. Chem.
274,
2366-2371 24.
Rothblat, G. H.,
de la Llera-Moya, M.,
Atger, V.,
Kellner-Weibel, G.,
Williams, D. L.,
and Phillips, M. C.
(1999)
J. Lipid Res.
40,
781-796 25.
Sehayek, E.,
Ono, J. G.,
Shefer, S.,
Nguyen, L. B.,
Wang, N.,
Batta, A. K.,
Salen, G.,
Smith, J. D.,
Tall, A. R.,
and Breslow, J. L.
(1998)
Proc. Natl. Acad. Sci. U. S. A.
95,
10194-10199 26.
Morton, R. E.,
and Zilversmit, D. B.
(1981)
J. Biol. Chem.
256,
11992-11995 27.
Le, N. A.,
Ramakrishnan, R.,
Dell, R. B.,
Ginsberg, H. N.,
and Brown, W. V.
(1986)
Methods. Enzymol.
129,
384-395[Medline]
[Order article via Infotrieve]
28.
Bligh, E. G.,
and Dyer, W. J.
(1959)
Can. J. Biochem. Physiol.
37,
911-917
29.
Rinninger, F.,
and Pittman, R. C.
(1987)
J. Lipid Res.
28,
1313-1315[Abstract]
30.
Honkakoski, P.,
and Negishi, M.
(1998)
Biochem. J.
330,
889-895
31.
Schwartz, C. C.,
Vlahcevic, Z. R.,
Berman, M.,
Meadows, J. G.,
Nisman, R. M.,
and Swell, L.
(1982)
J. Clin. Invest.
70,
105-116
32.
Williamson, R.,
Lee, D.,
Hagaman, J.,
and Maeda, N.
(1992)
Proc. Natl. Acad. Sci. U. S. A.
89,
7134-7138 33.
Botham, K. M.,
and Bravo, E.
(1995)
Prog. Lipid Res.
34,
71-97[CrossRef][Medline]
[Order article via Infotrieve]
34.
Schwartz, C. C.,
Vlahcevic, Z. R.,
Halloran, L. G.,
Gregory, D. H.,
Meek, J. B.,
and Swell, L.
(1975)
Gastroenterology
69,
1379-1382[Medline]
[Order article via Infotrieve]
35.
Bravo, E.,
and Cantafora, A.
(1990)
Biochim. Biophys. Acta
1045,
74-80[Medline]
[Order article via Infotrieve]
36.
Acton, S. L.,
Scherer, P. E.,
Lodish, H. F.,
and Krieger, M.
(1994)
J. Biol. Chem.
269,
21003-21009 37.
Johnson, W. J.,
Mahlberg, F. H.,
Rothblat, G. H.,
and Phillips, M. C.
(1991)
Biochim. Biophys. Acta
1085,
273-298[Medline]
[Order article via Infotrieve]
38.
Deleted in proof
39.
Elferink, R. P.,
Tytgat, G. N.,
and Groen, A. K.
(1997)
FASEB J.
11,
19-28[Abstract]
40.
Smit, J. J.,
Schinkel, A. H.,
Oude Elferink, R. P.,
Groen, A. K.,
Wagenaar, E.,
van Deemter, L.,
Mol, C. A.,
Ottenhoff, R.,
van der Lugt, N. M.,
van Roon, M. A.,
van der Valk, M. A.,
Offerhaus, G. J. A.,
Berns, A. J. M.,
and Borst, P.
(1993)
Cell
75,
451-462[CrossRef][Medline]
[Order article via Infotrieve]
41.
Verkade, H. J.,
Vonk, R. J.,
and Kuipers, F.
(1995)
Hepatology
21,
1174-1189[CrossRef][Medline]
[Order article via Infotrieve]
42.
Gerloff, T.,
Stieger, B.,
Hagenbuch, B.,
Madon, J.,
Landmann, L.,
Roth, J.,
Hofmann, A. F.,
and Meier, P. J.
(1998)
J. Biol. Chem.
273,
10046-10050 43.
de la Llera-Moya, M.,
Rothblat, G. H.,
Connelly, M. A.,
Kellner-Weibel, G.,
Sakr, S. W.,
Phillips, M. C.,
and Williams, D. L.
(1999)
J. Lipid Res.
40,
575-580 44.
Webb, N. R.,
Connell, P. M.,
Graf, G. A.,
Smart, E. J.,
de Villiers, W. J.,
de Beer, F. C.,
and van der Westhuyzen, D. R.
(1998)
J. Biol. Chem.
273,
15241-15248 45.
Gu, X.,
Trigatti, B.,
Xu, S.,
Acton, S.,
Babitt, J.,
and Krieger, M.
(1998)
J. Biol. Chem.
273,
26338-26348 46.
Connelly, M. A.,
Klein, S. M.,
Azhar, S.,
Abumrad, N. A.,
and Williams, D. L.
(1999)
J. Biol. Chem.
274,
41-47 47.
Smart, E. J.,
Ying, Y.,
Donzell, W. C.,
and Anderson, R. G.
(1996)
J. Biol. Chem.
271,
29427-29435 48.
Fielding, P. E.,
and Fielding, C. J.
(1995)
Biochemistry
34,
14288-14292[CrossRef][Medline]
[Order article via Infotrieve]
49.
Fielding, C. J.,
Bist, A.,
and Fielding, P. E.
(1999)
Biochemistry
38,
2506-2513[CrossRef][Medline]
[Order article via Infotrieve]
50.
Babitt, J.,
Trigatti, B.,
Rigotti, A.,
Smart, E. J.,
Anderson, R. G.,
Xu, S.,
and Krieger, M.
(1997)
J. Biol. Chem.
272,
13242-13249 51.
Graf, G. A.,
Connell, P. M.,
van der Westhuyzen, D. R.,
and Smart, E. J.
(1999)
J. Biol. Chem.
274,
12043-12048 52.
Bravo, E.,
Botham, K. M.,
Mindham, M. A.,
Mayes, P. A.,
Marinelli, T.,
and Cantafora, A.
(1994)
Biochim. Biophys. Acta
1215,
93-102[Medline]
[Order article via Infotrieve]
53.
Schwartz, C. C.,
Vlahcevic, Z. R.,
Halloran, L. G.,
and Swell, L.
(1981)
Biochim. Biophys. Acta
663,
143-162[Medline]
[Order article via Infotrieve]
54.
Scobey, M. W.,
Johnson, F. L.,
and Rudel, L. L.
(1989)
Am. J. Physiol.
257,
G644-G652 55.
Deleted in proof
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|
|
|
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|
|
|
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|
|
|
|
|
|
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|
|
|
|
 |
|
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|
|
|
|
|
|
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|
|
|
|
 |
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
 |
|
 R. D. Goldfarb, T. S. Parker, D. M. Levine, D. Glock, I. Akhter, A. Alkhudari, R. J. McCarthy, E. M. David, B. R. Gordon, S. D. Saal, et al. Protein-free phospholipid emulsion treatment improved cardiopulmonary function and survival in porcine sepsis Am J Physiol Regulatory Integrative Comp Physiol, February 1, 2003; 284(2): R550 - R557. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. L. Silver A Carboxyl-terminal PDZ-interacting Domain of Scavenger Receptor B, Type I Is Essential for Cell Surface Expression in Liver J. Biol. Chem., September 6, 2002; 277(37): 34042 - 34047. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Hyogo, S. Roy, B. Paigen, and D. E. Cohen Leptin Promotes Biliary Cholesterol Elimination during Weight Loss in ob/ob Mice by Regulating the Enterohepatic Circulation of Bile Salts J. Biol. Chem., September 6, 2002; 277(37): 34117 - 34124. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. Liu and M. Krieger Highly Purified Scavenger Receptor Class B, Type I Reconstituted into Phosphatidylcholine/Cholesterol Liposomes Mediates High Affinity High Density Lipoprotein Binding and Selective Lipid Uptake J. Biol. Chem., September 6, 2002; 277(37): 34125 - 34135. [Abstract] [Full Text] [PDF]
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N. Mendez-Sanchez, V. Gonzalez, A. C. King-Martinez, H. Sanchez, and M. Uribe Plasma Leptin and the Cholesterol Saturation of Bile Are Correlated in Obese Women after Weight Loss J. Nutr., August 1, 2002; 132(8): 2195 - 2198. [Abstract] [Full Text] [PDF]
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G. Bouchard, D. Johnson, T. Carver, B. Paigen, and M. C. Carey Cholesterol gallstone formation in overweight mice establishes that obesity per se is not linked directly to cholelithiasis risk J. Lipid Res., July 1, 2002; 43(7): 1105 - 1113. [Abstract] [Full Text] [PDF]
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 A. R. Tall MIghty Mouse Circ. Res., February 22, 2002; 90(3): 244 - 245. [Full Text] [PDF]
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M. Fuchs, A. Hafer, C. Munch, F. Kannenberg, S. Teichmann, J. Scheibner, E. F. Stange, and U. Seedorf Disruption of the Sterol Carrier Protein 2 Gene in Mice Impairs Biliary Lipid and Hepatic Cholesterol Metabolism J. Biol. Chem., December 14, 2001; 276(51): 48058 - 48065. [Abstract] [Full Text] [PDF]
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S. T. Thuahnai, S. Lund-Katz, D. L. Williams, and M. C. Phillips Scavenger Receptor Class B, Type I-mediated Uptake of Various Lipids into Cells. INFLUENCE OF THE NATURE OF THE DONOR PARTICLE INTERACTION WITH THE RECEPTOR J. Biol. Chem., November 16, 2001; 276(47): 43801 - 43808. [Abstract] [Full Text] [PDF]
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 A. Cachefo, P. Boucher, C. Vidon, E. Dusserre, F. Diraison, and M. Beylot Hepatic Lipogenesis and Cholesterol Synthesis in Hyperthyroid Patients J. Clin. Endocrinol. Metab., November 1, 2001; 86(11): 5353 - 5357. [Abstract] [Full Text] [PDF]
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N. Xu, U. Ekstrom, and P. Nilsson-Ehle ACTH Decreases the Expression and Secretion of Apolipoprotein B in HepG2 Cell Cultures J. Biol. Chem., October 12, 2001; 276(42): 38680 - 38684. [Abstract] [Full Text] [PDF]
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L. Zhou and A. Nilsson Sources of eicosanoid precursor fatty acid pools in tissues J. Lipid Res., October 1, 2001; 42(10): 1521 - 1542. [Abstract] [Full Text] [PDF]
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 A.-Y. Tu and J. J. Albers Glucose Regulates the Transcription of Human Genes Relevant to HDL Metabolism: Responsive Elements for Peroxisome Proliferator-Activated Receptor Are Involved in the Regulation of Phospholipid Transfer Protein Diabetes, August 1, 2001; 50(8): 1851 - 1856. [Abstract] [Full Text] [PDF]
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S. F. Cai, R. J. Kirby, P. N. Howles, and D. Y. Hui Differentiation-dependent expression and localization of the class B type I scavenger receptor in intestine J. Lipid Res., June 1, 2001; 42(6): 902 - 909. [Abstract] [Full Text]
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 C. K. Garcia, G. Mues, Y. Liao, T. Hyatt, N. Patil, J. C. Cohen, and H. H. Hobbs Sequence Diversity in Genes of Lipid Metabolism Genome Res., June 1, 2001; 11(6): 1043 - 1052. [Abstract] [Full Text] [PDF]
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P. Mardones, V. Quiñones, L. Amigo, M. Moreno, J. F. Miquel, M. Schwarz, H. E. Miettinen, B. Trigatti, M. Krieger, S. VanPatten, et al. Hepatic cholesterol and bile acid metabolism and intestinal cholesterol absorption in scavenger receptor class B type I-deficient mice J. Lipid Res., February 1, 2001; 42(2): 170 - 180. [Abstract] [Full Text]
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K. N. Liadaki, T. Liu, S. Xu, B. Y. Ishida, P. N. Duchateaux, J. P. Krieger, J. Kane, M. Krieger, and V. I. Zannis Binding of High Density Lipoprotein (HDL) and Discoidal Reconstituted HDL to the HDL Receptor Scavenger Receptor Class B Type I. EFFECT OF LIPID ASSOCIATION AND APOA-I MUTATIONS ON RECEPTOR BINDING J. Biol. Chem., July 7, 2000; 275(28): 21262 - 21271. [Abstract] [Full Text] [PDF]
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W. Chen, D. L. Silver, J. D. Smith, and A. R. Tall Scavenger Receptor-BI Inhibits ATP-binding Cassette Transporter 1- mediated Cholesterol Efflux in Macrophages J. Biol. Chem., September 29, 2000; 275(40): 30794 - 30800. [Abstract] [Full Text] [PDF]
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P. G. Yancey, M. de la Llera-Moya, S. Swarnakar, P. Monzo, S. M. Klein, M. A. Connelly, W. J. Johnson, D. L. Williams, and G. H. Rothblat High Density Lipoprotein Phospholipid Composition Is a Major Determinant of the Bi-directional Flux and Net Movement of Cellular Free Cholesterol Mediated by Scavenger Receptor BI J. Biol. Chem., November 17, 2000; 275(47): 36596 - 36604. [Abstract] [Full Text] [PDF]
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N. Ohgami, R. Nagai, A. Miyazaki, M. Ikemoto, H. Arai, S. Horiuchi, and H. Nakayama Scavenger Receptor Class B Type I-mediated Reverse Cholesterol Transport Is Inhibited by Advanced Glycation End Products J. Biol. Chem., April 13, 2001; 276(16): 13348 - 13355. [Abstract] [Full Text] [PDF]
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D. L. Silver, N. Wang, X. Xiao, and A. R. Tall High Density Lipoprotein (HDL) Particle Uptake Mediated by Scavenger Receptor Class B Type 1 Results in Selective Sorting of HDL Cholesterol from Protein and Polarized Cholesterol Secretion J. Biol. Chem., June 29, 2001; 276(27): 25287 - 25293. [Abstract] [Full Text] [PDF]
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C.-P. Liang and A. R. Tall Transcriptional Profiling Reveals Global Defects in Energy Metabolism, Lipoprotein, and Bile Acid Synthesis and Transport with Reversal by Leptin Treatment in Ob/ob Mouse Liver J. Biol. Chem., December 21, 2001; 276(52): 49066 - 49076. [Abstract] [Full Text] [PDF]
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