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The 84‐kDa Form of Human Matrix Metalloproteinase‐9 Degrades Substance P and Gelatin
Author(s) -
Backstrom Jon R.,
Tökés Zoltán A.
Publication year - 1995
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.1995.64031312.x
Subject(s) - gelatinase , substance p , enzyme , matrix metalloproteinase , biochemistry , chemistry , neurokinin a , peptide , extracellular matrix , metalloproteinase , cleavage (geology) , gelatinase a , thermolysin , extracellular , biology , trypsin , neuropeptide , receptor , paleontology , fracture (geology)
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 k cat / K m of 170 m M −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 1–6 and SP 7–11 , which were derived from cleavage of the Gln 6 ‐Phe 7 bond. Minor products were also generated from cleavage of the Gly 9 ‐Leu 10 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 intercellular communication by altering the availability of bioactive peptides.