The 84-kDa form of human matrix metalloproteinase-9 degrades substance P and gelatin

J Neurochem. 1995 Mar;64(3):1312-8. doi: 10.1046/j.1471-4159.1995.64031312.x.

Abstract

Matrix metalloproteinase-9 (MMP-9) is secreted from cells and, once activated, is thought to degrade collagen in the extracellular matrix. Because collagen is not readily localized where neurons have been shown to produce MMP-9 in the human brain, the ability of this enzyme to degrade bioactive peptides was investigated with representative tachykinin peptides [substance P (SP), neurokinin A, neurokinin B, and kassinin]. Latent MMP-9 (94 kDa) was purified from the human cell line HL-60 and converted to an intermediary active form (84 kDa) with p-aminophenylmercuric acetate. This active form of MMP-9 degraded SP with a kcat/Km of 170 mM-1 min-1, which is 30-fold greater than the previously reported value for a representative collagen-derived peptide. The major digestion products were identified as SP and SP, which were derived from cleavage of the Gln6-Phe7 bond. Minor products were also generated from cleavage of the Gly9-Leu10 bond. The other representative tachykinin peptides were cleaved at rates > 10-fold slower than that of SP. The 84-kDa peptidase was also active as a gelatinase. Longer treatment of MMP-9 with p-aminophenylmercuric acetate caused the conversion of the 84-kDa enzyme to the established 68-kDa active form; however, the rate of SP degradation did not increase. Because MMP-9 is produced by neurons of the CNS, these results suggest a possible regulatory role for the enzyme in interacellular communication by altering the availability of bioactive peptides.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Cell Line
  • Collagenases / chemistry
  • Collagenases / metabolism*
  • Enzyme Activation
  • Gelatin / metabolism*
  • Humans
  • In Vitro Techniques
  • Kinetics
  • Matrix Metalloproteinase 9
  • Molecular Sequence Data
  • Molecular Weight
  • Substance P / chemistry
  • Substance P / metabolism*
  • Substrate Specificity

Substances

  • Substance P
  • Gelatin
  • Collagenases
  • Matrix Metalloproteinase 9