title: Apolipoprotein A-IV is a novel substrate for matrix metalloproteinases.
abstract: Screening of matrix metalloproteinase (MMP)-14 substrates in human plasma using a proteomics approach previously identified apolipoprotein A-IV (apoA-IV) as a novel substrate for MMP-14. Here, we show that among the tested MMPs, purified apoA-IV is most susceptible to cleavage by MMP-7, and that apoA-IV in plasma can be cleaved more efficiently by MMP-7 than MMP-14. Purified recombinant apoA-IV (44-kDa) was cleaved by MMP-7 into several fragments of 41, 32, 29, 27, 24, 22 and 19 kDa. N-terminal sequencing of the fragments identified two internal cleavage sites for MMP-7 in the apoA-IV sequence, between Glu(185) and Leu(186), and between Glu(262) and Leu(263). The cleavage of lipid-bound apoA-IV by MMP-7 was less efficient than that of lipid-free apoA-IV. Further, MMP-7-mediated cleavage of apoA-IV resulted in a rapid loss of its intrinsic anti-oxidant activity. Based on the fact that apoA-IV plays important roles in lipid metabolism and possesses anti-oxidant activity, we suggest that cleavage of lipid-free apoA-IV by MMP-7 has pathological implications in the development of hyperlipidemia and atherosclerosis.
authors.affiliation: Department of Biochemistry, College of Life Science and Biotechnology, Yonsei University, Seoul 120-749, Republic of Korea.
authors.forename: Ji Yoon
authors.initials: JY
authors.lastname: Park
authors.forename: Jun Hyoung
authors.initials: JH
authors.lastname: Park
authors.forename: Wookju
authors.initials: W
authors.lastname: Jang
authors.forename: In-Kwan
authors.initials: IK
authors.lastname: Hwang
authors.forename: In Ja
authors.initials: IJ
authors.lastname: Kim
authors.forename: Hwa-Jung
authors.initials: HJ
authors.lastname: Kim
authors.forename: Kyung-Hyun
authors.initials: KH
authors.lastname: Cho
authors.forename: Seung-Taek
authors.initials: ST
authors.lastname: Lee
mesh_terms: D001054:Apolipoproteins A / Q000378:metabolism*; D006801:Humans; D050356:Lipid Metabolism / Q000235:genetics; D053511:Matrix Metalloproteinase 14 / Q000235:genetics / Q000378:metabolism; D019278:Matrix Metalloproteinase 3 / Q000235:genetics / Q000378:metabolism; D020783:Matrix Metalloproteinase 7 / Q000235:genetics / Q000378:metabolism; D020782:Matrix Metalloproteinases / Q000235:genetics / Q000378:metabolism*
chemical_list: D001054:Apolipoproteins A; C022205:apolipoprotein A-IV; D020782:Matrix Metalloproteinases; D019278:Matrix Metalloproteinase 3; D020783:Matrix Metalloproteinase 7; D053511:Matrix Metalloproteinase 14