Prevention of phospholipase‐C induced aggregation of low density lipoprotein by amphipathic apolipoproteins

FEBS Letters

Liu, Hu¹  Scraba, Douglas G.²  Ryan, Robert O.¹ 

[1] Lipid and Lipoprotein Research Group, University of Alberta, Edmonton, Alberta, T6G 2S2, Canada;Department of Biochemistry, University of Alberta, Edmonton, Alberta, T6G 2S2, Canada

关键词: Lipoprotein;    Phospholipase;    Apolipoprotein;    Amphipathic;    Phospholipid;    Diacylglycerol;    DAG;    diacylglycerol;    apo;    apolipoprotein;    apoLp-III;    apolipophorin III;    PL-C;    phospholipase C;    LDL;    low density lipoprotein;    VLDL;    very low density lipoprotein;    HDLP;    high density lipophorin;    SDS-PAGE;    sodium dodecyl sulfate polyacrylamide gel electrophoresis.;   

DOI  :  10.1016/0014-5793(93)81730-N

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

Phospholipase C (PL-C) digestion of human low density lipoprotein (LDL) results in hydrolytic cleavage of the phosphocholine head group of phosphatidylcholine, thereby generating diacylglycerol. Loss of amphiphillic surface lipids and/or accumulation of diacylglycerol causes LDL samples to develop turbidity. Examination of PL-C treated LDL by electron microscopy revealed a progressive aggregation of LDL as a function of phosphatidylcholine hydrolysis: fused particles, clusters, and multiple stacked aggregates were observed. Lipid analysis of untreated and aggregated LDL confirmed that the phosphatidylcholine content of the latter had decreased with a corresponding increase in diacylglycerol. It is likely that phospholipolysis created hydrophobic gaps within the surface monolayer of LDL, thereby inducing LDL fusion and aggregation. When amphipathic α-helix-containing apolipoproteins, such as human apoA-I or Manduca sexta apolipophorin III (apoLp-III) were present, PL-C treated LDL did not aggregate. Compositional analysis of apolipoprotein-containing PL-C LDL showed that phospholipolysis was not affected by the presence of apolipoproteins. Sodium dodecyl sulfate polyacrylamide gel electrophoresis of lipoproteins re-isolated following incubation with PL-C revealed an association of apoA-I or apoLp-III with PL-C digested LDL. Electron microscopy showed no major morphological differences between native LDL and apoprotein stabilized PL-C treated LDL and the average particle diameter of apoA-I stabilized PL-C LDL was 22.5 ± 0 2.2 nm versus 22.8 ± 1.6 nm for control LDL. Incubation of tritium-labeled apoLp-III with LDL and PL-C demonstrated that association of apoLp-III with PL-C LDL correlated with the extent of phospholipid hydrolysis, the apolipoproteins apparently being recruited to compensate for the increased hydrophobic surface created by conversion of phosphatidylcholine into diacylglycerol. The results suggest that transient association of amphipathic apolipoproteins with damaged or unstable LDL may provide a mechanism to obviate formation of atherogenic LDL aggregates in vivo.

【 授权许可】

Unknown