Membrane type-1 metalloproteinase mediates nitric oxide-induced activation of matrix metalloproteinase-13.
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.
Guo
Ai
A
Department of Orthopedics, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, PR China.
Yang
Lin
L
Gu
Jun-Chao
JC
D045744:Cell Line, Tumor; D019902:Chondrocytes / Q000378:metabolism*; D004789:Enzyme Activation / Q000502:physiology; D006801:Humans; D020781:Matrix Metalloproteinase 1 / Q000378:metabolism*; D053509:Matrix Metalloproteinase 13 / Q000378:metabolism*; D009569:Nitric Oxide / Q000502:physiology*; D011994:Recombinant Proteins / Q000378:metabolism
D011994:Recombinant Proteins; D009569:Nitric Oxide; D053509:Matrix Metalloproteinase 13; D020781:Matrix Metalloproteinase 1