In vivo glucosylated LpA-I subfraction. Evidence for structural and functional alterations.
This study compared the structural and functional properties of glucosylated and non-glucosylated LpA-I particle subfractions (GLpA-I and NGLpA-I, respectively) isolated from patients with poorly controlled type 1 (insulin-dependent) diabetes. Compared with NGLpA-I, GLpA-I showed an enrichment in triglycerides (P < .05) and a depletion in phospholipid (P < .05) content. Moreover, the triglycerides-to-cholesteryl esters ratio was increased (P < .05), suggesting an increased cholesteryl ester transfer protein activity and a possible transport defect that accelerates atherogenesis. The surface-to-core constituents ratio, an indirect estimate of particles size, is lower in GLpA-I (P < .01) than in NGLpA-I, correlating well with a larger median size (P < .05) as seen by electron microscopy. The apolipoprotein (apo) A-I conformation was evaluated through determination of the immunological accessibility of three different domains defining specific epitopes for anti-apo A-I monoclonal antibodies. We observed a marked decreased accessibility for two of these regions, which interestingly have already been implicated in the interaction with cells. Cell culture data suggest that nonenzymatic glycosylation occurring on apo A-I can modify lipoprotein function, since it results in a decreased binding of GLpA-I to HeLa cells and impaired cholesterol efflux from Fu5AH rat hepatoma cells.
Igau
B
B
Serlia et INSERM U325-1, Institut Pasteur de Lille, France.
Castro
G
G
Clavey
V
V
Slomianny
C
C
Bresson
R
R
Drouin
P
P
Fruchart
J C
JC
Fiévet
C
C
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D016632:Apolipoprotein A-I / Q000737:chemistry; D001667:Binding, Competitive; D002784:Cholesterol / Q000378:metabolism; D002788:Cholesterol Esters / Q000032:analysis; D003922:Diabetes Mellitus, Type 1 / Q000097:blood*; D000939:Epitopes / Q000276:immunology; D006031:Glycosylation; D006367:HeLa Cells / Q000378:metabolism; D006801:Humans; D017270:Lipoprotein(a) / Q000031:analogs & derivatives* / Q000737:chemistry / Q000276:immunology; D008114:Liver Neoplasms, Experimental / Q000473:pathology; D008297:Male; D010743:Phospholipids / Q000032:analysis; D011485:Protein Binding; D011487:Protein Conformation; D011499:Protein Processing, Post-Translational; D051381:Rats; D014280:Triglycerides / Q000032:analysis; D014407:Tumor Cells, Cultured
D000911:Antibodies, Monoclonal; D016632:Apolipoprotein A-I; D002788:Cholesterol Esters; D000939:Epitopes; D017270:Lipoprotein(a); D010743:Phospholipids; D014280:Triglycerides; C078260:lipoprotein A-I; D002784:Cholesterol