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

作者：Park Jun Hyoung; Park Sung Min; Park Ki Hoon; Cho Kyung Hyun; Lee Seung Taek^*

来源：Biochemical and Biophysical Research Communications, 2011, 409(1): 58-63.

DOI：10.1016/j.bbrc.2011.04.105

• Apolipoprotein A-I
• Cleavage site
• Lipid metabolism
• Matrix metalloproteinase
• Substrate

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.

• 出版日期2011-5-27