Apolipoprotein A-IV is a novel substrate for matrix metalloproteinases

Ji Yoon Park, Jun Hyoung Park, Wookju Jang, In Kwan Hwang, In Ja Kim, Hwa Jung Kim, Kyung Hyun Cho, Seung Taek Lee

Research output: Contribution to journalArticlepeer-review

15 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)291-298
Number of pages8
JournalJournal of Biochemistry
Volume151
Issue number3
DOIs
Publication statusPublished - 2012 Mar

Bibliographical note

Funding Information:
Studies on Ubiquitome Functions (2005-2001143, to S.-T.L.); the Mid-Career Researcher Program (2010-0026103, to S.-T.L.); the National Core Research Center Program (2010-006123, to H.-J.K.) of the National Research Foundation, the Ministry of Education, Science, and Technology, Republic of Korea and the National R&D Program for Cancer Control (1120110, to S.-T.L.) of the Ministry of Health and Welfare, Republic of Korea. Pre-doctoral trainee program recipients from the Brain Korea 21 Program from the Ministry of Education, Science, and Technology, Republic of Korea (to J.Y.P. and J.H.P.). Post-doctoral trainee program award from the Yonsei University Research Fund (to J.H.P.).

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology

Fingerprint Dive into the research topics of 'Apolipoprotein A-IV is a novel substrate for matrix metalloproteinases'. Together they form a unique fingerprint.

Cite this