Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:4.2.2.7 (heparinase)
 1,270 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Co-signaling events between integrins and cell surface proteoglycans play a critical role in the organization of the cytoskeleton and adhesion forces of cells. These processes, which appear to be responsible for maintaining intraocular pressure in the human eye, involve a novel cooperative co-signaling pathway between alpha5beta1 and alpha4beta1 integrins and are independent of heparan sulfate proteoglycans. Human trabecular meshwork cells isolated from the eye were plated on type III 7-10 repeats of fibronectin (alpha5beta1 ligand) in the absence or presence of the heparin (Hep) II domain of fibronectin. In the absence of the Hep II domain, cells had a bipolar morphology with few focal adhesions and stress fibers. The addition of the Hep II domain increased cell spreading and the numbers of focal adhesions and stress fibers. Cell spreading and stress fiber formation were not mediated by heparan sulfate proteoglycans because treatment with chlorate, heparinase, or soluble heparin did not prevent Hep II domain-mediated cell spreading. Cell spreading and stress fiber formation were mediated by alpha4beta1 integrin because soluble anti-alpha4 integrin antibodies inhibited Hep II domain-mediated cell spreading and soluble vascular cell adhesion molecule-1 (alpha4beta1 ligand)-induced cell spreading. This is the first demonstration of the Hep II domain mediating cell spreading and stress fiber formation through alpha4beta1 integrin. This novel pathway demonstrates a cooperative, rather than antagonistic, role between alpha5beta1 and alpha4beta1 integrins and suggests that interactions between the Hep II domain and alpha4beta1 integrin could modulate the strength of cytoskeleton-mediated processes in the trabecular meshwork of the human eye.
 ...
PMID:Heparin II domain of fibronectin uses alpha4beta1 integrin to control focal adhesion and stress fiber formation, independent of syndecan-4. 1557 66

We evaluated the effects of three specific glycosaminoglycan-degrading enzymes, chondroitinase ABC, testicular hyaluronidase, and heparinase, on the intraocular pressure (IOP) and the anterior chamber structures of bovine eyes. The anterior segment of freshly enucleated bovine eyes was perfused in a modified organ culture system. After each enzyme solution or its corresponding vehicle was introduced into the anterior chamber, the IOP was monitored for </=6 h. Compared to the control group, the chondroitinase ABC-treated group showed a significant IOP reduction after 1 h of perfusion. Testicular hyaluronidase and heparinase did not show any significant effect. Light microscopy revealed that chondroitinase ABC and testicular hyaluronidase induced detachment of the endothelial cells from trabecular beams in the uveal meshwork. Disruption of the tissues in the juxtacanalicular region and fragmentation of the endothelial cells facing the angular aqueous plexus were observed in the chondroitinase ABC- and heparinase-treated specimens. Electron microscopic study revealed detachment of trabecular meshwork cells from the beams and rupture of the inner wall of the aqueous plexus in all the enzyme-treated eyes. Cellular organelles and architectures were better preserved in chondroitinase ABC-treated eyes than those treated with hyaluronidase and heparinase. These results indicate that chondroitinase ABC has a pronounced effect on the IOP with relatively minor effect on the trabecular meshwork structures.
 ...
PMID:Effects of glycosaminoglycan-degrading enzymes on bovine trabecular meshwork in organ culture. 1992 Apr 91