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MMP‐2 inhibits PCSK9‐induced degradation of the LDL receptor in Hepa1‐c1c7 cells
Author(s) -
Wang Xiang,
Berry Evan,
Hernandez-Anzaldo Samuel,
Sun Difei,
Adijiang Ayinuer,
Li Liang,
Zhang Dawei,
Fernandez-Patron Carlos
Publication year - 2015
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2015.01.007
Subject(s) - ldl receptor , pcsk9 , kexin , proprotein convertase , matrix metalloproteinase , receptor , endocytosis , chemistry , microbiology and biotechnology , western blot , lipoprotein , biology , cholesterol , biochemistry , gene
Low‐density lipoprotein receptor (LDLR) catalyzes the uptake of LDL‐cholesterol by liver and peripheral organs. The function of the LDLR is antagonized by pro‐protein convertase subtilisin/kexin type 9 (PCSK9), which binds to LDLR at the plasma membrane inducing LDLR degradation. Here, we report that matrix metalloproteinase‐2 (MMP‐2) interacts with and cleaves PCSK9, as evidenced by proteomic, chemical cross‐linkage, blue native‐PAGE and domain‐specific antibodies Western blot analyses. Furthermore, MMP‐2 overexpression renders Hepa1‐c1c7 cells resistant to PCSK9‐induced LDLR degradation. The data suggest that pathological MMP‐2 overexpression may protect the LDLR from PCSK‐9‐induced degradation.