title: MMP-2 inhibits PCSK9-induced degradation of the LDL receptor in Hepa1-c1c7 cells.
abstract: 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.
authors.affiliation: Department of Biochemistry, University of Alberta, Edmonton, Alberta, Canada; Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: Xiang
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Biochemistry, University of Alberta, Edmonton, Alberta, Canada; Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: Evan
authors.initials: E
authors.lastname: Berry
authors.affiliation: Department of Biochemistry, University of Alberta, Edmonton, Alberta, Canada; Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: Samuel
authors.initials: S
authors.lastname: Hernandez-Anzaldo
authors.affiliation: Department of Chemistry, University of Alberta, Edmonton, Alberta, Canada; Faculty of Science, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: Difei
authors.initials: D
authors.lastname: Sun
authors.affiliation: Group on Molecular and Cell Biology of Lipids, University of Alberta, Edmonton, Alberta, Canada; Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: Ayinuer
authors.initials: A
authors.lastname: Adijiang
authors.affiliation: Department of Chemistry, University of Alberta, Edmonton, Alberta, Canada; Faculty of Science, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: Liang
authors.initials: L
authors.lastname: Li
authors.affiliation: Department of Biochemistry, University of Alberta, Edmonton, Alberta, Canada; Group on Molecular and Cell Biology of Lipids, University of Alberta, Edmonton, Alberta, Canada; Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: Dawei
authors.initials: D
authors.lastname: Zhang
authors.affiliation: Department of Biochemistry, University of Alberta, Edmonton, Alberta, Canada; Mazankowski Alberta Heart Institute, University of Alberta, Edmonton, Alberta, Canada; Cardiovascular Research Group, University of Alberta, Edmonton, Alberta, Canada; Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Alberta, Canada. Electronic address: cf2@ualberta.ca.
authors.forename: Carlos
authors.initials: C
authors.lastname: Fernandez-Patron
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002460:Cell Line; D020778:Matrix Metalloproteinase 2 / Q000502:physiology*; D051379:Mice; D008969:Molecular Sequence Data; D000071449:Proprotein Convertase 9; D043484:Proprotein Convertases / Q000502:physiology*; D059748:Proteolysis; D011973:Receptors, LDL / Q000378:metabolism*; D012697:Serine Endopeptidases / Q000502:physiology*
chemical_list: D011973:Receptors, LDL; C472126:Pcsk9 protein, mouse; D000071449:Proprotein Convertase 9; D043484:Proprotein Convertases; D012697:Serine Endopeptidases; D020778:Matrix Metalloproteinase 2; C522362:Mmp2 protein, mouse
keywords: Atherosclerosis; Cholesterol; Low density lipoprotein receptor; Matrix metalloproteinase-2; Pro-protein convertase subtilisin/kexin type 9; Sterol-regulatory element binding protein