Rapid removal to the liver of intravenously injected lipoprotein lipase

Wallinder, Lars; Bengtsson, Gunilla; Olivecrona, Thomas

doi:10.1016/0005-2760(79)90142-5

Cited by 51 publications

(19 citation statements)

References 24 publications

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“…It is known that LPL is cleared by the liver, and that heparin slows down this process (Wallinder et al, 1979;Peterson et al, 1985;Chajek-Shaul et al, 1988a;Vilaro et al, 1988). To explore the role of the liver in determining the different plasma LPL activities after low-Mr compared with conventional heparin, we used the supradiaphragmatic rat model described by Bezman-Tarcher & Robinson (1965).…”

Section: Resultsmentioning

confidence: 99%

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Low-Mr heparin is as potent as conventional heparin in releasing lipoprotein lipase, but is less effective in preventing hepatic clearance of the enzyme

Liu

Bengtsson‐Olivecrona

Østergaard

et al. 1991

Biochemical Journal

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This study compares a low-Mr heparin preparation with conventional heparin with respect to its interaction with lipoprotein lipase (LPL) in vitro and its effects on the enzyme in vivo. Both heparin preparations were polydisperse in binding to LPL, but on average the low-Mr preparation showed lower affinity. Thus both conventional and low-Mr heparin bound quantitatively to immobilized LPL, and were eluted as broad peaks when a salt gradient was applied, but the peak for low-Mr heparin was shifted towards lower salt concentrations. To displace LPL from immobilized heparin a higher concentration of low-Mr than of conventional heparin was needed. Injection of the low-Mr heparin into intact rats resulted in lower plasma LPL activity than did injection of an equal mass of conventional heparin, but when the liver was excluded from the circulation both heparin preparations resulted in similar plasma LPL activities. In perfused rat hearts, low-Mr heparin had at least the same effect on the release of LPL activity as did conventional heparin. In perfused livers, on the other hand, low-Mr heparin was less effective than conventional heparin in preventing the rapid uptake of exogenous labelled LPL. Hence the apparently lower average affinity of low-Mr heparin for LPL does not result in a demonstrably lower potency to release the enzyme from endothelial binding sites in peripheral tissues, but does result in a substantially decreased effect on the hepatic clearance of the enzyme.

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Section: Resultsmentioning

confidence: 99%

“…LPL is normally cleared from the circulating blood by the liver (Wallinder et al, 1979(Wallinder et al, , 1984Vilaro et al, 1988;Chajek-Shaul et al, 1988a). This is a very efficient process; in the rat more than 500/ of perfused LPL is removed by the liver in a single pass (Vilaro et al., 1988;Chajek-Shaul et al, 1988a).…”

Section: Introductionmentioning

confidence: 99%

Low-Mr heparin is as potent as conventional heparin in releasing lipoprotein lipase, but is less effective in preventing hepatic clearance of the enzyme

Liu

Bengtsson‐Olivecrona

Østergaard

et al. 1991

Biochemical Journal

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“…However, in situ no saturation of lipoprotein lipase binding was observed in perfused rat hearts [21], indicating that, at least in hearts, the binding sites for lipoprotein lipase are not fully occupied under normal conditions. Lipoprotein lipase can also be bound to the liver in a nonsaturable manner, and binding of lipoprotein lipase to the liver is considered as part of the degradation route of lipoprotein lipase [22][23][24]. Additionally, binding of lipoprotein lipase to the liver may play a role in the uptake of lipoproteins by the liver [25][26][27][28].…”

Section: Introductionmentioning

confidence: 99%

Rat liver contains a limited number of binding sites for hepatic lipase

Schoonderwoerd

Verhoeven

Jansen

1994

Biochemical Journal

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The binding of hepatic lipase to rat liver was studied in an ex vivo perfusion model. The livers were perfused with media containing partially purified rat hepatic lipase or bovine milk lipoprotein lipase. The activity of the enzymes was determined in the perfusion media before and after passage through the liver. During perfusion with a hepatic-lipase-containing medium the lipase activity in the medium did not change, indicating that there was no net binding of lipase by the liver. In contrast, more than 80% of the lipoprotein .lipase was removed from the medium. This lipoprotein lipase activity could be recovered into the perfusion medium completely by heparin perfusion of the liver. If livers, first depleted of hepatic lipase by heparin, were subsequent perfused with a hepatic-lipase-containing medium, 90 + 24 m-units of the lipase activity was bound per g of liver (up to 1000 m-units/total liver). However, heparin treatment of the liver decreases the ability of the liver to re-bind hepatic lipase by 80 %. Perfusion of rat livers with 0.3 M NaCl released 60 % of the lipase activity into the medium. Upon subsequent perfusion of these livers with hepatic-lipase-containing media, 541 + 164 munits of hepatic lipase could be bound per g of liver (up to 5000 m-units/total liver). The binding of hepatic lipase was also studied in livers of corticotropin (ACTH)-pre-treated rats. In these rats also, hepatic lipase bound only to livers which had been pre-perfused with heparin or 0.3 M NaCl. After heparin pre-perfusion, 88 + 12 m-units of hepatic lipase could be bound per g of liver, similar to that with livers of control rats not treated with ACTH. After prior salt perfusion, however, the capacity of the livers of ACTH-pre-treated rats to bind hepatic lipase was 212 + 60 m-units/g of liver. This is less than in livers of control rats (541 + 164 m-units/g of liver). These results indicate that in rat liver the binding ofhepatic lipase is heterogeneous in character and consists of heparin-resistant and heparin-sensitive components. The hepatic-lipase binding capacity of the liver is saturable and fully utilized under various conditions. The heparin-sensitive binding capacity is lowered in ACTH-treated rats, whereas the heparin-resistant binding is unaffected. We postulate that the functional hepatic lipase activity can be regulated by changes in the binding capacity of the liver.

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“…It was hypothesized that endothelial cells internalize LPL, store it in a non-lysosomal acidic compartment (endocytotic vesicle), and then recycle the LPL either to the medium or the cell surface (21). Based on the present study showing that apoB-expressing CHO cells degrade only a small portion of LPL and our recent observation that endothelial cells have NTAB (6,8), we hypothesize that apoB on the surface of endothelial cells provides a high affinity LPL-binding site that stabilizes LPL activity and delays its release into the bloodstream and eventual catabolism in the liver (33).…”

mentioning

confidence: 99%

Cell-surface Expression of an Amino-terminal Fragment of Apolipoprotein B Increases Lipoprotein Lipase Binding to Cells

Pang

Pillarisetti

Goldberg

1996

Journal of Biological Chemistry

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Previous studies (Sivaram, P., Choi, S. Y., Curtiss, L. K., and Goldberg, I. J. (1994) J. Biol. Chem. 269, 9409 -9412) from this laboratory showed that the NH 2 -terminal region of apoB (NTAB) has binding domains for lipoprotein lipase (LPL). LPL binding to endothelial cells, we hypothesize, involves interaction both with heparan sulfate proteoglycans and with a protein that has homology to NTAB. To test whether cell-surface NTAB would increase the amount and affinity of LPL binding to cells, we produced stable Chinese hamster ovary cell lines that have NTAB anchored to the cell surface. A cDNA encoding the amino-terminal 17% of apoB (apoB17) was fused to a cDNA coding for the last 37 amino acids of decay-accelerating factor (DAF), which contains the signal for glycosylphosphatidylinositol anchor attachment. Lipoprotein lipase (LPL)1 hydrolyzes triglycerides in the circulating plasma lipoproteins, chylomicrons, and very low density lipoproteins (1). Although LPL is synthesized by adipocytes, myocytes, and neurons, its primary site of action is at the luminal side of the endothelium. It is widely believed that LPL binds to endothelial cells via an electrostatic interaction with heparan sulfate proteoglycans (HSPG) (2-5). Earlier studies from this laboratory suggested that LPL binding to endothelial cells also involves a 116-kDa non-proteoglycan LPL-binding protein (6, 7). The 116-kDa LPL-binding protein has homology to the NH 2 -terminal region of apoB (NTAB) (8), the major structural protein of LDL, very low density lipoproteins, and chylomicrons (9). Furthermore, we have recently demonstrated that endothelial cells synthesize a full-length apoB protein and process it to generate the 116-kDa LPL-binding fragment (10).Several lines of evidence suggested that LPL interacts with NTAB. Ligand blotting of apoB fragments generated by thrombin digestion of LDL showed that labeled LPL bound specifically to NTAB. In addition, LPL bound to NH 2 -terminal fragments obtained from apoB-transfected CHO cells (8). 125I-LPL binding to endothelial cells was inhibited by antibodies to NH 2 -terminal regions of apoB, but not by antibodies that recognize epitopes closer to the carboxyl terminus of apoB. Based on these data, it was hypothesized that NTAB mediates LPL binding to cells and may confer specificity to LPL binding to endothelial cells.The amino-terminal region of apoB is relatively hydrophilic. Models of LDL suggest that NTAB extends away from the lipid core (9). Similarly, NTAB on the surface of a cell would not be expected to be buried within the cellular phospholipid bilayer and thus should be available to interact with LPL. Cells that overexpress truncated apoB fragments have been generated by other investigators. These cells, however, either secrete the small NH 2 -terminal fragments of apoB or degrade them intracellularly (11-13). Thus, these cells cannot be used to assess cell-surface actions of NTAB. Decay-accelerating factor (DAF) is a 70-kDa protein that contains sequences for glycosylphosphatidylinositol (GPI)...

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Rapid removal to the liver of intravenously injected lipoprotein lipase

Cited by 51 publications

References 24 publications

Low-Mr heparin is as potent as conventional heparin in releasing lipoprotein lipase, but is less effective in preventing hepatic clearance of the enzyme

Low-Mr heparin is as potent as conventional heparin in releasing lipoprotein lipase, but is less effective in preventing hepatic clearance of the enzyme

Rat liver contains a limited number of binding sites for hepatic lipase

Cell-surface Expression of an Amino-terminal Fragment of Apolipoprotein B Increases Lipoprotein Lipase Binding to Cells

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