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 journalArticle

13 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 1

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Matrix Metalloproteinases
Matrix Metalloproteinase 7
Substrates
Matrix Metalloproteinase 14
Lipids
Oxidants
apolipoprotein A-IV
Plasma (human)
Hyperlipidemias
Lipid Metabolism
Proteomics
Atherosclerosis
Screening
Plasmas

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology

Cite this

Park, J. Y., Park, J. H., Jang, W., Hwang, I. K., Kim, I. J., Kim, H. J., ... Lee, S-T. (2012). Apolipoprotein A-IV is a novel substrate for matrix metalloproteinases. Journal of Biochemistry, 151(3), 291-298. https://doi.org/10.1093/jb/mvr137
Park, Ji Yoon ; Park, Jun Hyoung ; Jang, Wookju ; Hwang, In Kwan ; Kim, In Ja ; Kim, Hwa Jung ; Cho, Kyung Hyun ; Lee, Seung-Taek. / Apolipoprotein A-IV is a novel substrate for matrix metalloproteinases. In: Journal of Biochemistry. 2012 ; Vol. 151, No. 3. pp. 291-298.
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Park, JY, Park, JH, Jang, W, Hwang, IK, Kim, IJ, Kim, HJ, Cho, KH & Lee, S-T 2012, 'Apolipoprotein A-IV is a novel substrate for matrix metalloproteinases', Journal of Biochemistry, vol. 151, no. 3, pp. 291-298. https://doi.org/10.1093/jb/mvr137

Apolipoprotein A-IV is a novel substrate for matrix metalloproteinases. / Park, Ji Yoon; Park, Jun Hyoung; Jang, Wookju; Hwang, In Kwan; Kim, In Ja; Kim, Hwa Jung; Cho, Kyung Hyun; Lee, Seung-Taek.

In: Journal of Biochemistry, Vol. 151, No. 3, 01.03.2012, p. 291-298.

Research output: Contribution to journalArticle

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Park JY, Park JH, Jang W, Hwang IK, Kim IJ, Kim HJ et al. Apolipoprotein A-IV is a novel substrate for matrix metalloproteinases. Journal of Biochemistry. 2012 Mar 1;151(3):291-298. https://doi.org/10.1093/jb/mvr137