Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.24.35 (matrix metalloproteinase 9)
 2,207 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cerebral infarction initiates a cascade of molecular events, leading to proteolytic cell death. Matrix-degrading metalloproteinases (MMPs) are neutral proteases involved in extracellular matrix damage. Type IV collagenase is an MMP that increases cerebral capillary permeability after intracerebral injection and may be important along with plasminogen activators (PA) in secondary brain edema in stroke. Therefore, we measured MMPs and PAs in spontaneously hypertensive (SHR) or Wistar-Kyoto (WKY) rats with permanent middle cerebral artery occlusion (MCAO). Brain tissue was assayed for MMPs and PAs at 1, 3, 12, and 24 h and 5 days after occlusion, using substrate gel polyacrylamide electrophoresis (zymography). SHR showed an increase in 92-kDa type IV collagenase (gelatinase B) in the infarcted hemisphere compared with the opposite side at 12 and 24 h (p < 0.05). Gelatinase A remained the same in both infarcted and normal tissue until 5 days after injury, when it increased significantly (p < 0.05). Urokinase-type PA was increased significantly at 12 and 24 h and 5 days, while tissue-type PA was decreased significantly at 1, 12, and 24 h in the ischemic compared with the nonischemic hemisphere. Gelatinase B was markedly increased in SHR at 12 and 24 h compared with WKY (p < 0.05). Secondary vasogenic edema is maximal 1-2 days after a stroke, which is the time that gelatinase B was elevated. The time of appearance of gelatinase B suggests a role in secondary tissue damage and vasogenic edema, while gelatinase A may be involved in tissue repair.
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PMID:Proteolytic cascade enzymes increase in focal cerebral ischemia in rat. 862 40

Membrane vesicles are shed by tumor cells both in vivo and in vitro. Although their functions are not well understood, it has been proposed that they may play multiple roles in tumor progression. We characterized membrane vesicles from human HT1080 fibrosarcoma cell cultures for the presence of proteinases involved in tumor invasion. By gelatin zymography and Western blotting, these vesicles showed major bands corresponding to the zymogen and active forms of gelatinase B (MMP-9) and gelatinase A (MMP-2) and to the MMP-9. tissue inhibitor of metalloproteinase 1 complex. Both gelatinases appeared to be associated with the vesicle membrane. HT1080 cell vesicles also showed a strong, plasminogen-dependent fibrinolytic activity in 125I fibrin assays; this activity was associated with urokinase plasminogen activator, as shown by casein zymography and Western blotting. Urokinase was bound to its high affinity receptor on the vesicle membrane. Addition of plasminogen resulted in activation of the progelatinases associated with the vesicles, indicating a role of the urokinase-plasmin system in MMP-2 and MMP-9 activation. We propose that vesicles shed by tumor cells may provide a large membrane surface for the activation of membrane-associated proteinases involved in extracellular matrix degradation and tissue invasion.
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PMID:Urokinase plasminogen activator and gelatinases are associated with membrane vesicles shed by human HT1080 fibrosarcoma cells. 920 45