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- Title
Apolipoprotein A-IV is a novel substrate for matrix metalloproteinases.
- Authors
Park, Ji Yoon; Park, Jun Hyoung; Jang, Wookju; Hwang, In-Kwan; Kim, In Ja; Kim, Hwa-Jung; Cho, Kyung-Hyun; Lee, Seung-Taek
- 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 Glu185 and Leu186, and between Glu262 and Leu263. 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.
- Subjects
METALLOPROTEINS; APOLIPOPROTEIN A; PROTEOMICS; HYPERLIPIDEMIA; NUCLEOTIDE sequence
- Publication
Journal of Biochemistry, 2012, Vol 151, Issue 3, p291
- ISSN
0021-924X
- Publication type
Article
- DOI
10.1093/jb/mvr137