Malondialdehyde adducts to, and fragmentation of, apolipoprotein B from human plasma.
Many recent in vitro experiments support the hypothesis that oxidatively modified low density lipoproteins (LDLs) could participate in atherogenesis. Oxidation of LDLs, especially derivatization by aldehydes originating from peroxidation of fatty acids and fragmentation of apolipoprotein (apo) B-100 which is their major apolipoprotein, probably occurs extravascularly and the presence of oxidized LDLs in the circulation is not well documented. Using electrophoresis and immunodetection techniques, we studied the structure of apo B and the presence of adducts of malondialdehyde (MDA) to this protein in LDLs from plasma of a limited population of five healthy subjects and nine patients with severe atherosclerosis. In the patient-derived LDLs, apo B appeared extensively fragmented, much more so than in those from the healthy subjects, although LDLs were isolated in all cases in the presence of antioxidants, protease inhibitors and antibiotics. Additionally, in all healthy subjects, we found a minor fragment of apo B-100, apo B-74, whereas the complementary peptide, apo B-26, was not detected; thus the presence of this minor form cannot be related to cleavage of apo B-100, either by proteolysis or by oxidation. We also present evidence that MDA adducts are present in circulating apo B and most of its fragments not only in atheromatous patients, but also in healthy subjects. Our results are consistent with the existence of oxidized LDLs in the human circulation. However, the role of non-oxidative phenomena in the structural modifications affecting apo B which are reported here cannot be excluded.
Lecomte
E
E
Laboratoire du Centre de Médecine Préventive, URA CNRS 597, Vandoeuvre Les Nancy, France.
Artur
Y
Y
Chancerelle
Y
Y
Herbeth
B
B
Galteau
M M
MM
Jeandel
C
C
Siest
G
G
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001055:Apolipoproteins B / Q000737:chemistry / Q000378:metabolism*; D001161:Arteriosclerosis / Q000097:blood; D005260:Female; D006801:Humans; D015227:Lipid Peroxidation; D008077:Lipoproteins, LDL / Q000097:blood; D008297:Male; D008315:Malondialdehyde / Q000097:blood*; D008875:Middle Aged; D015394:Molecular Structure; D010084:Oxidation-Reduction; D010446:Peptide Fragments / Q000097:blood
D001055:Apolipoproteins B; D008077:Lipoproteins, LDL; D010446:Peptide Fragments; C055664:apolipoprotein B-74; D008315:Malondialdehyde