MMP‐2 inhibits PCSK9‐induced degradation of the LDL receptor in Hepa1‐c1c7 cells
pmid: 25613181
MMP‐2 inhibits PCSK9‐induced degradation of the LDL receptor in Hepa1‐c1c7 cells
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.
- University of Alberta Canada
Low density lipoprotein receptor, Molecular Sequence Data, Serine Endopeptidases, Pro-protein convertase subtilisin/kexin type 9, Atherosclerosis, Sterol-regulatory element binding protein, Cell Line, Mice, Cholesterol, Matrix metalloproteinase-2, Receptors, LDL, Proteolysis, Animals, Matrix Metalloproteinase 2, Amino Acid Sequence, Proprotein Convertases, Proprotein Convertase 9
Low density lipoprotein receptor, Molecular Sequence Data, Serine Endopeptidases, Pro-protein convertase subtilisin/kexin type 9, Atherosclerosis, Sterol-regulatory element binding protein, Cell Line, Mice, Cholesterol, Matrix metalloproteinase-2, Receptors, LDL, Proteolysis, Animals, Matrix Metalloproteinase 2, Amino Acid Sequence, Proprotein Convertases, Proprotein Convertase 9
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