Analysis of apolipoprotein A-I as a substrate for matrix metalloproteinase-14

Jun Hyoung Park, Sung Min Park, Ki Hoon Park, Kyung Hyun Cho, Seung-Taek Lee

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Substrates for matrix metalloproteinase (MMP)-14 were previously identified in human plasma using proteomic techniques. One putative MMP-14 substrate was apolipoprotein A-I (apoA-I), a major component of high-density lipoprotein (HDL). In vitro cleavage assays showed that lipid-free apoA-I is a more accessible substrate for MMP-14 compared to lipid-bound apoA-I, and that MMP-14 is more prone to digest apoA-I than MMP-3. The 28-kDa apoA-I was cleaved into smaller fragments of 27, 26, 25, 22, and 14-kDa by MMP-14. ApoA-I sites cleaved by MMP-14 were determined by isotope labeling of C-termini derived from the cleavage and analysis of the labeled peptides by mass spectrometry, along with N-terminal sequencing of the fragments. Cleavage of apoA-I by MMP-14 resulted in a loss of ability to form HDL. Our results suggest that cleavage of lipid-free apoA-I by MMP-14 may contribute to reduced HDL formation, and this may be occurring during the development of various vascular diseases as lipid metabolism is disrupted.

Original languageEnglish
Pages (from-to)58-63
Number of pages6
JournalBiochemical and Biophysical Research Communications
Volume409
Issue number1
DOIs
Publication statusPublished - 2011 May 27

Fingerprint

Matrix Metalloproteinase 14
Apolipoprotein A-I
Substrates
HDL Lipoproteins
Lipids
Isotope Labeling
Plasma (human)
Matrix Metalloproteinase 3
Vascular Diseases
Lipid Metabolism
Isotopes
Proteomics
Labeling
Mass spectrometry
Assays
Mass Spectrometry
Peptides

All Science Journal Classification (ASJC) codes

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Park, Jun Hyoung ; Park, Sung Min ; Park, Ki Hoon ; Cho, Kyung Hyun ; Lee, Seung-Taek. / Analysis of apolipoprotein A-I as a substrate for matrix metalloproteinase-14. In: Biochemical and Biophysical Research Communications. 2011 ; Vol. 409, No. 1. pp. 58-63.
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Analysis of apolipoprotein A-I as a substrate for matrix metalloproteinase-14. / Park, Jun Hyoung; Park, Sung Min; Park, Ki Hoon; Cho, Kyung Hyun; Lee, Seung-Taek.

In: Biochemical and Biophysical Research Communications, Vol. 409, No. 1, 27.05.2011, p. 58-63.

Research output: Contribution to journalArticle

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