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Matrix Metalloproteinases in Dog Brains Exhibiting Alzheimer‐Like Characteristics
Author(s) -
Lim Giselle P.,
Russell Michael J.,
Cullen Michael J.,
Tökés Zoltán A.
Publication year - 1997
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.1471-4159.1997.68041606.x
Subject(s) - matrix metalloproteinase , zymography , amyloid (mycology) , gelatinase , hippocampus , chemistry , enzyme , amyloid precursor protein , alzheimer's disease , hippocampal formation , pathology , microbiology and biotechnology , biochemistry , biology , endocrinology , medicine , disease
We have previously reported that the amount of the neuronal matrix metalloproteinase (MMP) MMP‐9, capable of cleaving β‐amyloid 1–40 predominantly at Leu 34 ‐Met 35 , is increased in a latent form in hippocampal specimens from AD patients and have suggested that the lack of activation of this enzyme may contribute to the deposition of β‐amyloid in plaques. The current study addresses whether similar matrix proteinases are detectable in amyloid‐positive and ‐negative brain specimens of aged beagles. Using quantitative zymography, three major neutral proteinases with molecular masses of 60, 95, and 280 kDa were readily detected. These enzymes have the characteristics of MMPs because they were inhibited by EDTA and 1,10‐phenanthroline, and their activities were restored by addition of both Ca 2+ and Zn 2+ . The 95‐ and 280‐kDa proteinases cross‐reacted with specific monoclonal antibodies to human MMP‐9 (gelatinase B; EC 3.4.24.35). Canine MMP‐9 was latent because activation by organomercurial treatment resulted in a characteristic decrease in molecular mass. Statistical analysis revealed no difference in the 60‐kDa proteinase activity in amyloid‐positive and ‐negative brain specimens. However, significantly increased amounts of latent MMP‐9 were observed in amyloid‐positive brain specimens ( p ≤ 0.05) compared with amyloid‐negative brain specimens. The observations document that changes in MMP‐9 expression in amyloid‐positive beagle brains are similar to those reported in the human Alzheimer's disease hippocampus and suggest the possibility that insufficient activation of MMP‐9 may contribute to β‐amyloid accumulation, a hypothesis that needs to be further investigated.