Cardin AD

Cheung MC

Kunitake ST

Swaney JB

Apolipoprotein A-I-containing lipoproteins (high density lipoproteins, HDL) can be separated into two subfractions, which have pre-beta and alpha electrophoretic mobilities, respectively. These fractions differ in both composition and structure. Some preparations of pre-beta-migrating HDL, but not alpha-migrating HDL, were found to contain two polypeptides with Mr of approximately 26 and 14 kDa, which are scission products of apolipoprotein (apo) A-I. They are recognized by monospecific antibodies to apo A-I and have N-terminal sequences identical to those of mature apo A-I. This proteolytic scission of apo A-I occurs primarily after venipuncture. Immediate addition of protease inhibitors minimized the appearance of the fragments in plasma. To study the relative susceptibilities of pre-beta and alpha HDL to proteolysis, the lipoproteins were incubated in vitro with plasmin. The apo A-I in pre-beta HDL was extensively degraded, but that in alpha-migrating HDL was degraded to a much lesser extent, indicating that the appearance of apo A-I fragments in pre-beta HDL was due to enhanced sensitivity to proteolysis. To varying degrees, thrombin, kallikrein, elastase, arginine C endoprotease, and chymotrypsin also appear to cleave pre-beta HDL faster than alpha HDL. Most of the proteases generated a 12 to 14 kDa peptide fragment under conditions of limited cleavage. These results suggest that the conformational state of apo A-I in pre-beta-migrating HDL or its spatial relationship to lipids is significantly different from that of apo A-I in alpha-migrating HDL.(ABSTRACT TRUNCATED AT 250 WORDS)</jats:p

S T Kunitake

G C Chen

S F Kung

J W Schilling

D A Hardman

J P Kane

Crossref

Arteriosclerosis An Official Journal of the American Heart Association Inc

Pre-beta high density lipoprotein. Unique disposition of apolipoprotein A-I increases susceptibility to proteolysis.

Pre-beta high density lipoprotein. Unique disposition of apolipoprotein A-I increases susceptibility to proteolysis.

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