Scavenger receptor class B, type I mediates uptake of lipoprotein-associated phosphatidylcholine by primary porcine cerebrovascular endothelial cells

Sovic, Andrea; Balázs, Zoltán; Hrzenjak, Andelko; Reicher, Helga; Panzenboeck, Ute; Malle, Ernst; Sattler, Wolfgang

doi:10.1016/j.neulet.2004.04.097

Cited by 14 publications

(10 citation statements)

References 20 publications

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“…In monocytes, high affinity binding of LDL was shown to involve SR-BI that mediated the selective import of the major lipoprotein-associated phospholipids (34). A role for SR-BI in PC uptake from LDL and HDL by endothelial cells was also demonstrated by Sattler and co-workers (35).…”

supporting

confidence: 52%

“…A likely candidate for LDL-PC uptake is SR-BI, not only because SR-BI is a receptor for LDL (15, 16) but also because SR-BI is involved in LDL-phospholipid uptake in monocytes and cerebrovascular endothelial cells (34,35). Our results with SR-BI Ϫ/Ϫ cells and with a blocking anti-SR-BI antibody showed that 30% of LDL-PC is taken up by this receptor.…”

Section: Discussionmentioning

confidence: 77%

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Conversion of Low Density Lipoprotein-associated Phosphatidylcholine to Triacylglycerol by Primary Hepatocytes

Minahk

Kim

Nelson

et al. 2008

Journal of Biological Chemistry

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We have studied the uptake and metabolism of phosphatidylcholine (PC), the major phospholipid of low density lipoproteins (LDL), by cultures of primary hepatocytes. Strikingly, in the absence of the LDL receptor, PC incorporation into hepatocytes was inhibited by only 30%, whereas cholesteryl ether uptake was inhibited by 60 -70%. On the other hand, scavenger receptor class B, type I, the other important receptor for LDL in the liver, was found to be responsible for the uptake of the remaining 30 -40% of LDL-cholesteryl ether. PC uptake was, however, only partially inhibited (30%) in scavenger receptor class B, type I, knock-out hepatocytes. Once LDL-PC was taken up by hepatocytes, ϳ50% of LDL-[ 3 H]oleate-PC was converted to triacylglycerol rather than degraded in lysosomes as occurs for LDLderived cholesteryl esters. The remainder of the LDL-derived PC was not significantly metabolized to other products. Triacylglycerol synthesis from LDL-PC requires a PC-phospholipase C activity as demonstrated by inhibition with the phospholipase C inhibitor D609 or activation with rattlesnake venom. Small interfering RNA-mediated suppression of acyl-CoA:diacylglycerol acyltransferase 2 (DGAT2), but not DGAT1, decreased the acylation of the LDL-derived diacylglycerol. These findings show that PC in LDL particles is taken up not only by the classical receptors but also by additional mechanism(s) followed by metabolism that is completely different from the cholesteryl esters or apoB100, the other main components of LDL.

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supporting

confidence: 52%

Section: Discussionmentioning

confidence: 77%

Conversion of Low Density Lipoprotein-associated Phosphatidylcholine to Triacylglycerol by Primary Hepatocytes

Minahk

Kim

Nelson

et al. 2008

Journal of Biological Chemistry

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“…In line with this hypothesis is the observation that SR-BI mediates also the uptake of HDL phospholipids into cells (65)(66)(67). In cerebrovascular endothelial cells natural PC was selectively internalized from HDL by SR-BI (68). On the other hand, a slow and a fast exchanging component of HDL PC has been reported, and it is likely, that a large portion of PC will be co-transported with HDL apoprotein in hepatic cells (69).…”

Section: Discussionmentioning

confidence: 76%

Mathematical Analysis of Hepatic High Density Lipoprotein Transport Based on Quantitative Imaging Data

Wüstner

2005

Journal of Biological Chemistry

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Hepatocytes internalize high density lipoprotein (HDL) at the basolateral membrane. Most HDL is recycled while some is shuttled to the canalicular membrane by transcytosis. Here, transport of HDL was analyzed by mathematical modeling based on measurements in polarized hepatic HepG2 cells. Recycling of HDL from basolateral sorting endosomes was modeled by applying the rapid equilibrium approach. Analytical expressions were derived, which describe in one model the transport of HDL to the subapical compartment/apical recycling compartment, the biliary canaliculus (BC), and to late endosomes and lysosomes (LE/LYS). Apical endocytosis of HDL predicted by the model was confirmed for rhodamine-dextran and fluorescent asialoorosomucoid, markers for LE/LYS in living HepG2 cells. Budding of endocytic vesicles from the BC was directly observed by time lapse imaging of a fluorescent lipid probe. Based on fitted kinetic parameters and their covariance matrix a Monte Carlo simulation of HDL transport in hepatocytes was performed. The model was used to quantitatively assess release of HDL-associated free cholesterol by scavenger receptor BI. It is shown that only 6% of HDLassociated sterol reaches the BC as a constituent of the HDL particles, whereas the remaining sterol is rapidly released from HDL and shuttled to the BC by non-vesicular transport.Hepatic transport of high density lipoprotein (HDL) 1 and processing of its associated lipids including sterols is a key step during reverse cholesterol transport. Free cholesterol and cholesteryl esters (CE) are transferred from the HDL particle to the hepatocyte (1-3). Biliary secretion of cholesterol along with bile salts and phosphatidylcholine (PC) is the only pathway of sterol clearance from the body (4). Uptake of sterols from HDL in the hepatocyte is partially independent of the processing of the HDL protein moiety. This so-called selective uptake is mediated largely by the scavenger receptor BI (SR-BI) at the basolateral membrane of hepatic cells (3,5). It has been proposed that endocytosis and recycling of the whole HDL particle occurs in hepatocytes and contributes to selective CE uptake (6 -8). Recently, we demonstrated that the natural cholesterol analog dehydroergosterol (DHE) incorporated into fluorescent HDL is rapidly released from the lipoprotein at the basolateral membrane of polarized HepG2 cells (9). This process required SR-BI but was not dependent on metabolic energy in contrast to uptake of the HDL particles. DHE was rapidly shuttled to the apical canalicular membrane of HepG2 cells by ATP-independent non-vesicular transport (9, 10). The canalicular membrane of HepG2 cells forms apical closed vacuoles that resemble the biliary canaliculi (BC) of hepatocytes in many respects (11). We found evidence for internalization of DHE and fluorescent PC from the BC of HepG2 cells (10, 12). We demonstrated that fluorescent PC and DHE become delivered to a subapical compartment or apical recycling compartment (SAC/ ARC) in vesicles in 15-30 min. The identity of this SAC/A...

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“…Lipoprotein receptors from the LDL receptor family present on the surface of the cerebral capillary endothelial cells (Herz and Bock 2002;Herz 2001;Schneider and Nimpf 2003;Strickland et al 2002) may play an important role in the facilitation of transport of essential fatty acids and DHA to brain. HDLspecific receptors have also been identified on the surface of brain capillaries as well (Goti et al 2001;Panzenboeck et al 2002;Sovic et al 2004;Srivastava 2003). However, observations presented in this article point to a specific routing of DHA by liver into VLDL and LDL fractions.…”

Section: Brain Uptakementioning

confidence: 77%

Role of Liver and Plasma Lipoproteins in Selective Transport of n-3 Fatty Acids to Tissues: A Comparative Study of 14C-DHA and 3H-Oleic Acid Tracers

Polozova

Salem

2007

J Mol Neurosci

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We conducted a study aimed at a direct comparison of the plasma dynamics and uptake of docosahexaenoic (DHA) and oleic (OA) fatty acids by various organs. 14C-DHA and 3H-OA were intravenously co-injected into mice. At 5 min after injection, more than 40% of the 14C-DHA, but less than 20% of the 3H-OA, labels was associated with the liver. Heart uptake of 14C-DHA was three to four times greater compared to the 3H-OA label. Brain incorporation of 14C-DHA slowly rose to 0.7% at 24 h, but it remained at the 1-1.5% level for 3H-OA. Total 14C activity in plasma reached 2% of the injected dose at 20 min and leveled off at 0.5% after 1.5 h. Fifteen percent of 14C-DHA plasma activity at 30 min was associated with non-esterified fatty acids, whereas about 85% was recovered in triglycerides in very low-density lipoprotein (VLDL) and LDL fractions. Only 30% of 3H-OA derived activity was found in the VLDL fraction at 30 min. All 3H activity in plasma at later time points was in catabolite fractions. These findings demonstrate that liver plays an important role in the initial selectivity for DHA. It is likely that DHA is specifically taken up by liver, esterified, loaded into lipoproteins, and then delivered to brain, heart, and other target tissues.

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Scavenger receptor class B, type I mediates uptake of lipoprotein-associated phosphatidylcholine by primary porcine cerebrovascular endothelial cells

Cited by 14 publications

References 20 publications

Conversion of Low Density Lipoprotein-associated Phosphatidylcholine to Triacylglycerol by Primary Hepatocytes

Conversion of Low Density Lipoprotein-associated Phosphatidylcholine to Triacylglycerol by Primary Hepatocytes

Mathematical Analysis of Hepatic High Density Lipoprotein Transport Based on Quantitative Imaging Data

Role of Liver and Plasma Lipoproteins in Selective Transport of n-3 Fatty Acids to Tissues: A Comparative Study of 14C-DHA and 3H-Oleic Acid Tracers

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