Proteolytic degradation of low-density lipoprotein by lipoprotein(a) and by recombinant apo(a).
The plasma concentration of lipoprotein(a) (Lp(a)) is correlated with the risk of atherosclerosis, and both Lp(a) and LDL are present in atherosclerotic lesions. Lp(a) is similar in structure to LDL, its distinguishing feature from LDL being the presence of one additional glycoprotein, apo(a), that is linked to apoB-100. Upon incubation of 125I-LDL with isolated Lp(a), we found a dose and time-dependent increase in the proportion of TCA-soluble radioactive material, demonstrating degradation of LDL. The addition of unlabelled LDL decreased the degradation of 125I-LDL, while HDL or albumin had no such effect. Recombinant DNA-derived apo(a), R-apo(a), which itself expressed no amidolytic activity, displayed an increase in amidolytic activity after pre-incubation with LDL. Furthermore, activated R-apo(a) caused degradation of 125I-LDL. Treatment of R-apo(a) with phenylmethanesulfonyl fluoride inhibited LDL apoB-100 degradation, indicating that R-apo(a) has serine esterase type proteolytic activity. The results show that apo(a) is activated in the presence of LDL, and that this activation leads to proteolytic modification of LDL. The induction of apo(a) proteolytic activity by LDL suggests a novel mechanism whereby Lp(a) may be atherogenic.
Pursiainen
M
M
National Public Health Institute, Department of Biochemistry, Helsinki, Finland.
Jauhiainen
M
M
Kovanen
P T
PT
Ehnholm
C
C
D000595:Amino Acid Sequence; D053299:Apolipoprotein B-100; D001053:Apolipoproteins / Q000378:metabolism*; D001055:Apolipoproteins B / Q000378:metabolism; D053241:Apoprotein(a); D001161:Arteriosclerosis / Q000209:etiology; D001665:Binding Sites; D002863:Chromogenic Compounds / Q000737:chemistry; D010450:Endopeptidases / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D017270:Lipoprotein(a) / Q000378:metabolism*; D008077:Lipoproteins, LDL / Q000378:metabolism*; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000737:chemistry; D011994:Recombinant Proteins / Q000378:metabolism; D013379:Substrate Specificity
D053299:Apolipoprotein B-100; D001053:Apolipoproteins; D001055:Apolipoproteins B; D002863:Chromogenic Compounds; D017270:Lipoprotein(a); D008077:Lipoproteins, LDL; D009842:Oligopeptides; D011994:Recombinant Proteins; D010450:Endopeptidases; D053241:Apoprotein(a)