Cleavage and functional loss of human apolipoprotein E by digestion of matrix metalloproteinase-14

Hyoung Park Jun, Sung Min Park, Sun Hyun Park, Kyung Hyun Cho, Seung Taek Lee

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

By means of a degradomic approach applying proteomic techniques, we previously suggested that apolipoprotein E (apoE) is a substrate of matrix metalloproteinase-14 (MMP-14). Here we confirm that apoE is, in fact, a substrate of MMP-14 and also of MMP-7 and MMP-2 to a lesser extent. The 34 kDa apoE protein was initially processed by MMP-14 into fragments with molecular masses of 28, 23, 21, and 11 kDa. MMP-14 cleavage sites within the apoE protein were determined by C-terminal labeling of MMP-14-digested apoE fragments with isotope (18O/16O = 1:1) and identification of the doublet fragments or peptides showing 2 Da difference by MS, along with N-terminal sequencing of the fragments. It was determined that the primary MMP-14 cleavage sites were A176-I177, P183-L184, P202-L203, and Q249-T250. The MMP-14-mediated cleavage of apoE was consistent regardless of whether apoE existed in its lipid-bound or lipid-free form. Upon digestion with MMP-14, apoE loses its ability to suppress the platelet-derived growth factor-induced migration of rat vascular smooth muscle cells. Considering the important role of apoE for lipid metabolism and atherosclerosis protection, our findings suggest that MMP-14 plays an essential role for the development of hyperlipidemia and atherosclerosis as a result of degradation of apoE.

Original languageEnglish
Pages (from-to)2926-2935
Number of pages10
JournalProteomics
Volume8
Issue number14
DOIs
Publication statusPublished - 2008 Jul 1

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Matrix Metalloproteinase 14
Apolipoproteins E
Digestion
Matrix Metalloproteinases
Atherosclerosis
Lipids
Peptide Fragments
Platelet-Derived Growth Factor
Molecular mass
Substrates
Hyperlipidemias
Vascular Smooth Muscle
Lipid Metabolism
Isotopes
Proteomics
Labeling
Smooth Muscle Myocytes
Muscle
Rats
Proteins

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology

Cite this

Jun, Hyoung Park ; Park, Sung Min ; Park, Sun Hyun ; Cho, Kyung Hyun ; Lee, Seung Taek. / Cleavage and functional loss of human apolipoprotein E by digestion of matrix metalloproteinase-14. In: Proteomics. 2008 ; Vol. 8, No. 14. pp. 2926-2935.
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Cleavage and functional loss of human apolipoprotein E by digestion of matrix metalloproteinase-14. / Jun, Hyoung Park; Park, Sung Min; Park, Sun Hyun; Cho, Kyung Hyun; Lee, Seung Taek.

In: Proteomics, Vol. 8, No. 14, 01.07.2008, p. 2926-2935.

Research output: Contribution to journalArticle

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