Hydrogen peroxide-mediated, lysyl oxidase-dependent chemotaxis of vascular smooth muscle cells.
Lysyl oxidase (LO), an enzyme secreted by vascular smooth muscle cells (VSMC), initiates the covalent crosslinking of polypeptide chains within collagen and elastin. The present study reveals that purified LO strongly induces directional migration of VSMC in an in vitro assay system. LO-dependent chemotaxis, but not chemokinesis, was abolished by beta-aminopropionitrile, an active site inhibitor of LO, or by catalase, as well as by prior heat denaturation. This indicates that the H(2)O(2) product of amine oxidation by LO is critical to the expression of its chemotactic activity. The results indicate that the chemotactic response requires direct access between LO and a substrate molecule (or molecules) tightly associated with the VSMC. The addition of LO to VSMC elevated the levels of intracellular H(2)O(2), enhanced stress fiber formation, and focal adhesion assembly, is consistent with the induction of the chemotactic response.
Li
W
W
Department of Microbiology, Boston University School of Medicine, Boston, Massachusetts 02118, USA.
Liu
G
G
Chou
I N
IN
Kagan
H M
HM
D008841:Actin Cytoskeleton / Q000201:enzymology; D000629:Aminopropionitrile / Q000494:pharmacology; D000818:Animals; D001011:Aorta / Q000201:enzymology / Q000378:metabolism; D002374:Catalase / Q000494:pharmacology; D002417:Cattle; D002448:Cell Adhesion / Q000187:drug effects; D002478:Cells, Cultured; D002633:Chemotaxis / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D006861:Hydrogen Peroxide / Q000378:metabolism*; D008856:Microscopy, Fluorescence; D009131:Muscle, Smooth, Vascular / Q000201:enzymology* / Q000378:metabolism*; D008249:Protein-Lysine 6-Oxidase / Q000378:metabolism* / Q000494:pharmacology; D051381:Rats
D000629:Aminopropionitrile; D006861:Hydrogen Peroxide; D002374:Catalase; D008249:Protein-Lysine 6-Oxidase