Interaction of lipoprotein lipase with phospholipid vesicles: effect on protein and lipid structure

McLean, Larry R.; Larsen, William J.; Jackson, Richard L.

doi:10.1021/bi00352a020

Cited by 16 publications

(5 citation statements)

References 42 publications

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“…The functional integrity of apoA‐I and the PL composition of HDL are important determinants affecting the particle's capability to promote cellular cholesterol efflux [6–8,38]. In the present study we have observed impaired cholesterol efflux from J774 macrophages to (reagent or enzymatically generated) OCl − ‐modified HDL.…”

Section: Discussionsupporting

confidence: 51%

Hypochlorite modification of high density lipoprotein: effects on cholesterol efflux from J774 macrophages

Bergt¹,

Reicher²,

Malle³

et al. 1999

FEBS Letters

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The present study was aimed at investigating effects of hypochlorite (HOCl) modification of high density lipoproteins subclass 3 (HDL 3 ) on their ability for cellular cholesterol removal from permanent J774 macrophages. Our findings indicate that HOCl (added as reagent or generated enzymatically by the myeloperoxidase/H 2 O 2 /Cl 3 system) damages apolipoprotein A-I, the major protein component of HDL 3 . Fatty acid analysis of native and HOCl-modified HDL 3 revealed that unsaturated fatty acids in both major lipid subclasses (phospholipids and cholesteryl esters) are targets for HOCl attack. HOCl modification resulted in impaired HDL 3 -mediated cholesterol efflux from J774 cells, regardless of whether reagent or enzymatically generated HOCl was used to modify the lipoprotein. Decreased cholesterol efflux was also observed after HOCl modification of reconstituted HDL particles. Impairment of cholesterol efflux from macrophages was noticed at low and physiologically occurring HOCl concentrations.z 1999 Federation of European Biochemical Societies.

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Section: Discussionsupporting

confidence: 51%

Hypochlorite modification of high density lipoprotein: effects on cholesterol efflux from J774 macrophages

Bergt¹,

Reicher²,

Malle³

et al. 1999

FEBS Letters

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“…We hypothesize that along the endothelial surface, LpL engages a large triglyceride carrier, generates FFA, and causes transient reductions in pH. As reported elsewhere (59,60), the interaction of LpL with model lipoproteins is fairly tight and such a cooperative binding to several LpL molecules would hold the chylomicron firmly at the lipolysis sites. These interactions may also produce a protected compartment that excludes plasma perfusion.…”

Section: Discussionsupporting

confidence: 58%

Lipolysis-induced iron release from diferric transferrin: possible role of lipoprotein lipase in LDL oxidation

Balagopalakrishna

Paka

Pillarisetti

et al. 1999

Journal of Lipid Research

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Conditions leading to oxidation of LDL in vivo are still unknown. While the occurrence of oxidized lipoproteins and catalytic free iron in advanced atherosclerotic lesions has been demonstrated, the origin of both is unclear. In vivo, iron metabolism is tightly regulated by ironbinding proteins that ensure that virtually no free iron exists. We examined whether physiological events such as lipolysis might reduce pH, facilitate iron release from transferrin (Tf), and promote low density lipoprotein (LDL) oxidation. Lipolysis is brought about by lipoprotein lipase (LpL), a triglyceride hydrolase present on endothelial cell surfaces and in atherosclerotic lesions. LpL hydrolysis of Intralipid lowered pH from 7.40 to 7.00 in 10% human serum and from 7.40 to 6.88 in phosphate-buffered saline. Similar decreases in pH were also observed when very low density lipoproteins were hydrolyzed by LpL. Lipolysis was accompanied by a 2-fold increase in the release of 59 Fe from Tf. Tf binding to subendothelial matrix (SEM), a site of key events in atherosclerosis, increased 2-fold as the pH decreased from 7.40 to 6.00. More free iron also bound to SEM as the pH decreased below 7.40. We next tested whether a reduction in pH promotes LDL oxidation. More oxidation products were found in LDL incubated at low pH for 24 h in 10% human serum. Malonaldehyde contents (nmol/mg protein), measured as TBARS, were 7.11 ؎ 0.34 at pH 7.40, 7.65 ؎ 0.49 at pH 7.00, 9.00 ؎ 1.18 at pH 6.50, and 11.54 ؎ 0.63 at pH 6.00. Based on these results, we hypothesize that lipolysis-induced acidic conditions enhance iron release from Tf and increase formation of oxidized LDL. -Balagopalakrishna, C., L. Paka, S. Pillarisetti, and I. J. Goldberg. Lipolysis-induced iron release from diferric transferrin: possible role of lipoprotein lipase in LDL oxidation.

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“…Yet they are rapidly delipidated by LPL in vivo, and calculations based on the turnover number of the enzyme show that many LPL molecules must act simultaneously on the particle (8). The interaction of soluble LPL with model lipoproteins is fairly tight (30). Hence, cooperative binding to several LPL molecules would hold the chylomicron firmly at endothelial-binding-lipolysis sites.…”

Section: Discussionmentioning

confidence: 99%

Fatty acid control of lipoprotein lipase: a link between energy metabolism and lipid transport.

Peterson

Bihain

Bengtsson‐Olivecrona

et al. 1990

Proc. Natl. Acad. Sci. U.S.A.

209

134

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Lipoprotein lipase (LPL) catalyzes the fluxgenerating step in transport of fatty acids from lipoprotein triacylglycerols into tissues for use in metabolic reactions. In viro studies have shown that fatty acids can bind to the enzyme and impede its other interactions. In this study we have searched for evidence of fatty acid control of LPL in vivo by rapid infusion of a triacylglycerol emulsion to healthy volunteers. During infusion the activity of LPL but not of hepatic lipase increased in plasma, but to different degrees in different individuals. The time course for the increase in LPL activity differed from that for triacylglycerols but followed the plasma levels of free fatty acids. This was true during infusions and when the emulsion was given as a bolus iijection. In particular there were several instances when plasma triacylglycerol levels were very high but free fatty acids and LPL activity remained low. Model studies with bovine LPL showed that fatty acids displace the enzyme from heparin-agarose. We suggest that in situations when fatty acids are generated more rapidly by LPL than they are used by the local tissue, they cause dissociation of the enzyme from its binding to endothelial heparan sulfate and are themselves released into circulation.Triacylglycerol (TG) transport is a major pathway in energy metabolism and handles more than 100 g of lipid per day in individuals on a typical Western diet. The TGs are unloaded from the lipoproteins through hydrolysis by lipoprotein lipase (LPL) at the vascular endothelium in extrahepatic tissues (for review, see refs. 1 and 2). It is generally assumed that the rate-limiting factor is the amount of LPL available at the endothelium (3). In support of this, studies in animals have shown a correlation between the activity of LPL in a tissue and its uptake of fatty acids from chylomicra (1,2,4). Inherent in this view is the assumption that the tissue can assimilate the fatty acids at the rate that the enzyme provides them. The possibility that fatty acid assimilation can be rate-limiting has been raised (5) but has received little attention. In vitro studies have, however, shown that LPL has a built-in mechanism for product control. The enzyme can bind fatty acids, which reduces its affinity for lipid droplets (6, 7) as well as for heparin-like polysaccharides (8) and abolishes the activation by apolipoprotein C-II (9). This suggests that accumulation of fatty acids at the endothelium might inhibit further lipolysis and disrupt the binding of LPL to heparan sulfate. Whether this mechanism ever comes into play in vivo is not known. To demonstrate it one would need a condition in which the clearing capacity was overloaded. In this study we have tried to create such a situation by rapid infusion of a lipid emulsion. Analyses. Blood samples (5 ml) were collected in EDTA and immediately put in ice water. Plasma was rapidly separated by centrifugation for 5 min at 1000 x g using a Beckman refrigerated centrifuge. Plasma lipids were determined by the following enzy...

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Interaction of lipoprotein lipase with phospholipid vesicles: effect on protein and lipid structure

Cited by 16 publications

References 42 publications

Hypochlorite modification of high density lipoprotein: effects on cholesterol efflux from J774 macrophages

Hypochlorite modification of high density lipoprotein: effects on cholesterol efflux from J774 macrophages

Lipolysis-induced iron release from diferric transferrin: possible role of lipoprotein lipase in LDL oxidation

Fatty acid control of lipoprotein lipase: a link between energy metabolism and lipid transport.

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