Apolipoprotein A-I-containing lipoproteins, with or without apolipoprotein A-II, as progenitors of pre-beta high-density lipoprotein particles.
Apolipoprotein A-I-(apoA-I-) containing lipoproteins isolated by immunoaffinity chromatography can be divided into two general subfractions on the basis of the presence [Lp(AI + AII)] or absence [Lp(AI - AII)] of apoA-II. The Lp(AI - AII) subfraction can be further subfractionated into two subgroups with pre-beta mobility as well as those of alpha mobility. We have characterized the Lp(AI - AII) and Lp(AI + AII) subfractions after the removal of pre-beta high-density lipoproteins (pre-beta-HDL) to compare only the two subfractions with alpha mobility. The Lp(AI - AII) and Lp(AI + AII) of alpha mobility, while both heterogeneous subfractions, share many gross features in common. Both subfractions were predominantly spherical in shape, had similar conformation of apoA-I as investigated by circular dichroism and specific endoproteases, and had similar contents of phospholipids, phospholipid species, triglycerides, and cholesterol ester. However, there was significantly less protein (-10%) and more free cholesterol (+46%) in the Lp(AI - AII) subfraction than in the Lp(AI + AII) subfraction. We investigated the generation of pre-beta-HDL from both the Lp(AI - AII) and Lp(AI + AII) subfractions during incubation with low-density lipoproteins and cholesteryl ester transfer protein. We found that both Lp(AI - AII) and Lp(AI + AII) subfractions were capable of generating pre-beta-HDL-like particles. Our results suggest that the formation of pre-beta-HDL involves dissociation of apoA-I from both Lp(AI - AII) and Lp(AI + AII) subfractions. These results refine a model describing the cycling of apoA-I between pre-beta-HDL and alpha-HDL linked to the movement of cholesteryl esters through HDL.
Cardiovascular Research Institute, University of California, San Francisco 94030-0130.
L K
LK
Hennessy
S T
ST
Kunitake
J P
JP
Kane
D016632:Apolipoprotein A-I / Q000378:metabolism*; D016633:Apolipoprotein A-II / Q000378:metabolism*; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D002942:Circular Dichroism; D005260:Female; D006801:Humans; D008074:Lipoproteins / Q000097:blood* / Q000737:chemistry; D008075:Lipoproteins, HDL / Q000097:blood*; D008297:Male; D008854:Microscopy, Electron; D010316:Particle Size; D011498:Protein Precursors / Q000097:blood
D016632:Apolipoprotein A-I; D016633:Apolipoprotein A-II; D008074:Lipoproteins; D008075:Lipoproteins, HDL; D011498:Protein Precursors