title: An inhibitor of the matrix metalloproteinase synthesized by rabbit corneal epithelium.
abstract: Normal and abnormal processes of cellular invasion often are initiated by degradation of basement membranes. The process of corneal ulceration might operate via similar mechanisms; degradation of the corneal stroma is not seen until after the basement membrane underlying the corneal epithelium in the preulcerative lesion is lost. Recent data implicate a member of the matrix metalloproteinase (MMP) family of enzymes, 92 kD gelatinase/type IV collagenase (MMP-9) in both cellular invasion processes and degradation of epithelial basement membrane before corneal ulceration. This suggests that use of nontoxic substances that block activity of MMP-9 might be useful in preventing or inhibiting pathologic invasion processes in vivo. An agent that fits these criteria is N-[D,L-2-isobutyl-3(N'-hydroxycarbonylamido)-propanoyl]-O- methyl-L-tyrosine methylamide, which previously has been characterized as an inhibitor of tumor cell collagenases. In this study, the authors show that the inhibitor can efficiently block activity of MMP-9 purified from cultures of rabbit corneal epithelial cells. Results suggest that the recently reported efficacy of a closely related inhibitor in blocking progression of alkali burns to ulceration might be attributable to its action against MMP-9.
authors.affiliation: Eye Research Institute, Harvard Medical School, Boston, Massachusetts.
authors.forename: M E
authors.initials: ME
authors.lastname: Fini
authors.forename: T Y
authors.initials: TY
authors.lastname: Cui
authors.forename: A
authors.initials: A
authors.lastname: Mouldovan
authors.forename: D
authors.initials: D
authors.lastname: Grobelny
authors.forename: R E
authors.initials: RE
authors.lastname: Galardy
authors.forename: S J
authors.initials: SJ
authors.lastname: Fisher
mesh_terms: D000577:Amides / Q000494:pharmacology*; D000818:Animals; D002478:Cells, Cultured; D002846:Chromatography, Affinity; D003315:Cornea / Q000201:enzymology*; D004151:Dipeptides; D004591:Electrophoresis, Polyacrylamide Gel; D004848:Epithelium / Q000201:enzymology; D005347:Fibroblasts / Q000201:enzymology; D005780:Gelatin / Q000378:metabolism; D006801:Humans; D020780:Matrix Metalloproteinase 9; D003012:Microbial Collagenase / Q000037:antagonists & inhibitors* / Q000302:isolation & purification; D011817:Rabbits; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000494:pharmacology
chemical_list: D000577:Amides; D004151:Dipeptides; C065557:N-(2-isobutyl-3-(N'-hydroxycarbonylamido)propanoyl)-O-methyltyrosinemethylamide; D014443:Tyrosine; D005780:Gelatin; D003012:Microbial Collagenase; D020780:Matrix Metalloproteinase 9