Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.24.23 (MMP)
 4,246 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Urokinase-type plasminogen activator (uPA) is a key serine protease involved in invasion and metastasis. We had shown that overproduction of uPA in tumor cells is controlled by a phospholipase D-protein kinase C-dependent pathway. Now we studied whether other signaling pathways participate in the regulation of constitutive uPA and metalloproteinase (MMP) overproduction in tumor cells. Staurosporine, a protein kinase inhibitor, stimulated uPA and MMP-9 secretion as measured by radial caseinolysis, zymography and Western blotting. Genistein, a specific tyrosine kinase inhibitor, reduced the constitutive and staurosporine-induced uPA and MMP-9 secretion. Interestingly, the phosphatase inhibitor vanadate stimulated uPA secretion. Verapamil, a calcium channel blocker, inhibited both endogenous and PMA-stimulated secretion of uPA but was unable to inhibit staurosporine-induced secretion. The alcohol n-butanol, a phospholipase D and protein kinase C inhibitor, besides inhibiting constitutive uPA secretion, blocked staurosporine-induced secretion. Our results suggest that constitutive and staurosporine-induced uPA and MMP-9 secretion by LM3 murine mammary tumor cells is controlled by an endogenous tyrosine kinase pathway and probably involves protein phosphatases. In addition, the staurosporine-induced signal regulating urokinase secretion is independent of extracellular calcium but dependent on phospholipase D.
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PMID:Secretion of urokinase and metalloproteinase-9 induced by staurosporine is dependent on a tyrosine kinase pathway in mammary tumor cells. 957 73

Increased levels of metalloproteinase (MMP)-9 have been shown in hypertensive patients. Lercanidipine is a calcium channel blocker with antioxidant actions. We examined whether lercanidipine produces antioxidant effects and reduces MMP-9 activity in hypertensive patients in a placebo-controlled, crossover, single-blinded design study including 18 healthy volunteers (control group), and 14 hypertensive patients without (N = 7) or with (N = 7) diabetes mellitus. Hypertensive patients were randomized to treatment with placebo (15 days) or lercanidipine 20 mg/d (15 days). Arterial blood pressure was evaluated with ambulatory blood pressure monitoring. Plasma thiobarbituric acid reactive species (TBA-RS) levels were measured to assess oxidative stress, and plasma MMP-2 and MMP-9 were assayed by gel zymography before and after treatment with placebo or lercanidipine. Plasma concentrations of tissue inhibitor of metalloproteinases (TIMP)-1 were measured by ELISA. Lercanidipine reduced mean arterial pressure by 7% in hypertensive patients without diabetes (P < 0.05), but not in hypertensive patients with diabetes. It significantly decreased plasma TBA-RS levels in hypertensive patients without and with diabetes (95% confidence interval [CI], -26 to -46%, P = 0.048, and -22 to -33%, P = 0.036, respectively). In addition, lercanidipine decreased activated MMP-9 in hypertensive patients without and with diabetes (95% CI, -19 to -47%, P = 0.047, and -80 to -96%, P = 0.010, respectively). No effects were seen on MMP-2. No significant differences or changes in plasma TIMP-1 concentrations were found. Therefore, we demonstrate for the first time that lercanidipine consistently decreased MMP-9 activity and reduced oxidative stress in hypertensive patients, thus suggesting a mechanism probably involved in the pleotropic actions of lercanidipine.
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PMID:Lercanidipine reduces matrix metalloproteinase-9 activity in patients with hypertension. 1642 95