Membrane type-1 metalloproteinase mediates nitric oxide-induced activation of matrix metalloproteinase-13. 2009

Ai Guo, and Lin Yang, and Jun-Chao Gu
Department of Orthopedics, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, PR China.

This article investigates the mechanism of activation of matrix metalloproteinase-13 induced by nitric oxide. SW1353 cells were stimulated with S-nitroso-N-acetyl-D,L-penicillamine, expressions and activities of metalloproteinase-13, and membrane type-1 metalloproteinase were assayed, and a proteolytic activation of recombinant human metalloproteinase-13 was measured in the presence of recombinant human membrane type-1 metalloproteinase. Nitric oxide increased expressions of both matrix metalloproteinases and stimulated the proteolytic processing of metalloproteinase-13 from the pro-enzyme to the final active form. Recombinant human membrane type-1 metalloproteinase was able to process recombinant human metalloproteinase-13 to fully active enzyme. S-nitroso-N-acetyl-D,L-penicillamine had no effect on recombinant human metalloproteinase-13 activity. Nitric oxide scavenger (OxyHb) strongly attenuated nitric oxide-induced proteolytic activation of metalloproteinase-13. Furthermore, tissue inhibitor of metalloproteinase-2 markedly reduced the activation of metalloproteinase-13 in response to nitric oxide. These studies identify membrane type-1 metalloproteinase as a target for nitric oxide, which may be critical for the nitric oxide-induced activation of metalloproteinase-13.

UI MeSH Term Description Entries
D009569 Nitric Oxide A free radical gas produced endogenously by a variety of mammalian cells, synthesized from ARGININE by NITRIC OXIDE SYNTHASE. Nitric oxide is one of the ENDOTHELIUM-DEPENDENT RELAXING FACTORS released by the vascular endothelium and mediates VASODILATION. It also inhibits platelet aggregation, induces disaggregation of aggregated platelets, and inhibits platelet adhesion to the vascular endothelium. Nitric oxide activates cytosolic GUANYLATE CYCLASE and thus elevates intracellular levels of CYCLIC GMP. Endogenous Nitrate Vasodilator,Mononitrogen Monoxide,Nitric Oxide, Endothelium-Derived,Nitrogen Monoxide,Endothelium-Derived Nitric Oxide,Monoxide, Mononitrogen,Monoxide, Nitrogen,Nitrate Vasodilator, Endogenous,Nitric Oxide, Endothelium Derived,Oxide, Nitric,Vasodilator, Endogenous Nitrate
D011994 Recombinant Proteins Proteins prepared by recombinant DNA technology. Biosynthetic Protein,Biosynthetic Proteins,DNA Recombinant Proteins,Recombinant Protein,Proteins, Biosynthetic,Proteins, Recombinant DNA,DNA Proteins, Recombinant,Protein, Biosynthetic,Protein, Recombinant,Proteins, DNA Recombinant,Proteins, Recombinant,Recombinant DNA Proteins,Recombinant Proteins, DNA
D004789 Enzyme Activation Conversion of an inactive form of an enzyme to one possessing metabolic activity. It includes 1, activation by ions (activators); 2, activation by cofactors (coenzymes); and 3, conversion of an enzyme precursor (proenzyme or zymogen) to an active enzyme. Activation, Enzyme,Activations, Enzyme,Enzyme Activations
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D045744 Cell Line, Tumor A cell line derived from cultured tumor cells. Tumor Cell Line,Cell Lines, Tumor,Line, Tumor Cell,Lines, Tumor Cell,Tumor Cell Lines
D053509 Matrix Metalloproteinase 13 A secreted matrix metalloproteinase that plays a physiological role in the degradation of extracellular matrix found in skeletal tissues. It is synthesized as an inactive precursor that is activated by the proteolytic cleavage of its N-terminal propeptide. Collagenase 3,Collagenase-3,MMP-13 Metalloproteinase,MMP13 Metalloproteinase,Matrix Metalloproteinase-13,MMP 13 Metalloproteinase,Metalloproteinase 13, Matrix,Metalloproteinase, MMP-13,Metalloproteinase, MMP13,Metalloproteinase-13, Matrix
D019902 Chondrocytes Polymorphic cells that form cartilage. Chondroblasts,Chondroblast,Chondrocyte
D020781 Matrix Metalloproteinase 1 A member of the metalloproteinase family of enzymes that is principally responsible for cleaving FIBRILLAR COLLAGEN. It can degrade interstitial collagens, types I, II and III. Interstitial Collagenase,MMP-1 Metalloproteinase,MMP1 Metalloproteinase,Matrix Metalloproteinase-1,Pro-Matrix Metalloproteinase-1,Promatrixmetalloproteinase-1,proMMP-1,MMP 1 Metalloproteinase,Metalloproteinase 1, Matrix,Metalloproteinase, MMP-1,Metalloproteinase, MMP1,Metalloproteinase-1, Pro-Matrix,Pro Matrix Metalloproteinase 1,Promatrixmetalloproteinase 1

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