Apolipoprotein A-II Inhibits High Density Lipoprotein Remodeling and Lipid-poor Apolipoprotein A-I Formation

Rye, Kerry Anne; Wee, Kevin; Curtiss, Linda K.; Bonnet, David J.; Barter, Philip J.

doi:10.1074/jbc.m213250200

Cited by 51 publications

(51 citation statements)

References 37 publications

(38 reference statements)

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“…The physiological role of apoA-II remains unclear. Experimental data indicate that apoA-II is likely to maintain the plasma HDL pool and enhance HDL stability by inhibiting hepatic lipase activity and CETP-mediated dissociation of lipid-poor apoA-I (17,18). It has been also shown that the rate of apoA-II production determines the distribution of apoA-I between HDL A-I and HDL A-I/A-II (19).…”

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confidence: 97%

Phospholipids mediated conversion of HDLs generates specific apoA-II pre-β mobility particles

Wróblewska

Kortas-Stempak

Szutowicz

et al. 2009

Journal of Lipid Research

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Apolipoproteins (apo)A-I and A-II are major proteins of human HDL. The cycling of apoA-I between lipidpoor and lipid-rich forms of HDL plays a key role in the transport of cholesterol by these particles. ApoA-II resides only in part of HDL particles, and little is known about its role in HDL metabolism. Our study investigates the redistribution of apoA-II after HDL remodelling induced by exogenous phospholipids (PL). During incubation with egg yolk lecithin (EYL) liposomes, human HDL became PL-enriched and free cholesterol (FC)-depleted, and lost small amounts of apoA-I and apoA-II. The loss of FC and apolipoproteins correlated with the rise of PL content in HDL. Agarose gel electrophoresis demonstrated the appearance of new pre-b mobility fractions containing apoA-I and apoA-II in liposomes and HDL mixtures. Two-dimensional nondenaturing 2-27% PAGE has shown that the pre-b mobility fraction that appeared at initial liposome-PL/HDL-PL ratio 5:1 consisted of two distinct heterogeneous subpopulations of particles containing either apoA-I or apoA-II. Our study provides evidence that during HDL conversion mediated by PL apoA-II dissociated from HDL particles yielding apoA-II-specific pre-b mobility particles. This observation supports the hypothesis that apoA-II in plasma, like apoA-I, may cycle between lipid-poor and lipid-rich forms of HDL.-Wróblewska, M., B. KortasStempak, A. Szutowicz, and T. Badzio. Phospholipids mediated conversion of HDLs generates specific apoA-II pre-b mobility particles. J. Lipid Res. 2009. 50: 667-675.

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confidence: 97%

Phospholipids mediated conversion of HDLs generates specific apoA-II pre-β mobility particles

Wróblewska

Kortas-Stempak

Szutowicz

et al. 2009

Journal of Lipid Research

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“…1.21 g/l) of human or murine plasma (unpublished observations). In our transgenic mice, hapoA-II associates with both large (10 nm) and small (7.8 nm) HDL particles, the latter predominant in the high-expressing l mice (7,8). It remains indeterminate whether in vivo HDL holoparticles filter through the glomerulus.…”

Section: Discussionmentioning

confidence: 99%

“…The generation of transgenic mice for hapoA-II has been previously described (7,8). The three lines, b, y, and l, were backcrossed for at least eight generations to strain C57BL/6J (IFFA-CREDO-Charles River).…”

Section: Animalsmentioning

confidence: 99%

“…The three lines, b, y, and l, were backcrossed for at least eight generations to strain C57BL/6J (IFFA-CREDO-Charles River). Transgenic mice were detected as described (7,8) and were hemizygous for the hapoA-II transgene. Male and female control and transgenic mice over 8 weeks of age were used in equal proportions in all studies.…”

Section: Animalsmentioning

confidence: 99%

“…EDTA-plasma was supplemented with 0.005% gentamycin-1 mM EDTA-0.04% Na-azide and protease inhibitors, and ultracentrifuged to prepare LDL and HDL as described (7,8). LDL and HDL protein contents were measured (24), and LDL and HDL were labeled with 1,1'-dioctadecyl-3,3,3 ¶,3 ¶-tetramethylindocarbocyanine (DiI) (25).…”

Section: Lipoproteins and Apolipoproteinsmentioning

confidence: 99%

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Apolipoprotein A-II is catabolized in the kidney as a function of its plasma concentration

Dugué-Pujol

Rousset

Château

et al. 2007

Journal of Lipid Research

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We investigated in vivo catabolism of apolipoprotein A-II (apo A-II), a major determinant of plasma HDL levels. Like apoA-I, murine apoA-II (mapoA-II) and human apoA-II (hapoA-II) were reabsorbed in the first segment of kidney proximal tubules of control and hapoA-II-transgenic mice, respectively. ApoA-II colocalized in brush border membranes with cubilin and megalin (the apoA-I receptor and coreceptor, respectively), with mapoA-I in intracellular vesicles of tubular epithelial cells, and was targeted to lysosomes, suggestive of degradation. By use of three transgenic lines with plasma hapoA-II concentrations ranging from normal to three times higher, we established an association between plasma concentration and renal catabolism of hapoA-II. HapoA-II was rapidly internalized in yolk sac epithelial cells expressing high levels of cubilin and megalin, colocalized with cubilin and megalin on the cell surface, and effectively competed with apoA-I for uptake, which was inhibitable by anti-cubilin antibodies. Kidney cortical cells that only express megalin internalized LDL but not apoA-II, apoA-I, or HDL, suggesting that megalin is not an apoA-II receptor. We show that apoA-II is efficiently reabsorbed in kidney proximal tubules in relation to its plasma concentration.-Dugué-Pujol, S

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