Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.24.17 (MMP-3)
 3,419 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Matrix metalloproteinases (MMPs) secreted by connective tissue cells are capable of acting on extracellular matrix components of glomerular basement membrane at a slow rate and thus may play a role in the control of protein permeability and in the progression of certain kinds of glomerulonephritis. We have used an in vitro assay to measure the direct effect of three MMPs and human neutrophil elastase on glomerular albumin permeability (Palbumin). Glomeruli were isolated from normal male Sprague-Dawley rats and suspended in isolation medium with or without interstitial collagenase, gelatinase-A, stromelysin-1, or elastase and were incubated at 37 degrees C for up to 4 hours. A tissue-specific inhibitor of matrix metalloproteinases (TIMP-1) and a plasma proteinase inhibitor, alpha2-macroglobulin (alpha2M), were used to block the activity of MMPs. Palbumin was calculated from the change in glomerular volume in response to an applied oncotic gradient. In this study stromelysin-1 (10 microg/ml) and elastase (5 microg/ml) increased Palbumin significantly. Stromelysin-1 increased Palbumin after 4 hours, whereas elastase had an effect after 2 hours. Lower concentrations of stromelysin-1 or shorter incubation time had no effect on Palbumin. Incubation for up to 4 hours with interstitial collagenase (10 microg/ml) or gelatinase-A (10 microg/ml) had no effect on Palbumin. Coincubation with TIMP-1 and alpha2M blocked the stromelysin-1-mediated increase in Palbumin. We conclude that stromelysin-1 is capable of affecting the glomerular filtration barrier directly and that it may play an important role in causing proteinuria in glomerular diseases.
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PMID:Matrix metalloproteinase (stromelysin-1) increases the albumin permeability of isolated rat glomeruli. 878 37

Monoamine-activated human alpha2-macroglobulin (alpha2M) has been previously demonstrated to inhibit TrkA-, TrkB-, and TrkC-mediated signal transduction. Rat alpha1-macroglobulin (alpha1M) and alpha2M are structural homologues of human alpha2M, but rat alpha1M is distinctly different from rat alpha2M in many ways and its role in the mammalian nervous system is unknown. In this report, monoamine-activated rat alpha1M was demonstrated to enhance in a dose-dependent manner nerve growth factor (NGF)-promoted neurite outgrowth in pheochromocytoma PC12 cells. Monoamine-activated alpha1M by itself, however, was neither neurotrophic nor mitogenic to PC12 cells. To investigate further its possible mode of action, the ability of monoamine-activated alpha1M and normal alpha1M to bind and to activate the NGF receptor (TrkA) was investigated. Monoamine-activated alpha1M formed a more stable complex with TrkA than normal alpha1 M, but the binding of monoamine-activated alpha1M to TrkA was adversely affected by prior stimulation of TrkA with NGF. In addition, monoamine-activated alpha1M enhanced the NGF-promoted TrkA phosphorylation and up-regulated the expression of NGF-inducible immediate-early genes (c-jun and NGFI-A) and delayed-response genes (SCG10 and transin) in PC12 cells; normal alpha1M, in contrast, produced little or no effect. This study demonstrates that alpha1M, the constitutive form of alpha-macroglobulin in the rat, possesses the ability to promote NGF-mediated differentiation in PC12 cells, possibly via its direct action on TrkA receptors and TrkA-mediated signal transduction and gene expression.
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PMID:Rat alpha1-macroglobulin enhances nerve growth factor-promoted neurite outgrowth, TrkA phosphorylation, and gene expression of pheochromocytoma PC12 cells. 1061 8

The proteolytic activity of proinflammatory matrix metalloproteinases (MMPs) is elevated in lipid-rich atherosclerotic plaques, thereby contributing to plaque fragility and rupture. We hypothesized that changes in circulating levels of MMPs and their specific inhibitors (TIMPs) could reflect the atherosclerotic process occurring within the arterial wall. We determined serum levels of MMP-3, MMP-9, TIMP-1 and TIMP-2 in dyslipidemic subjects and compared them to those of age- and sex-matched normolipidemic healthy controls. Serum levels of MMP-3, MMP-9 and TIMP-1 were significantly increased in hyperlipidemic subjects versus controls (+54, +29 and +15%, respectively; P<0.001). We also noted a trend to elevated serum MMP-3 levels in patients with atherosclerotic lesions when compared to patients free of atherosclerosis (P=0.07). Circulating levels of MMPs and TIMPs were associated neither with those of C-reactive protein, nor with those of alpha2-macroglobulin (a nonspecific MMP inhibitor), nor with intima-media thickness values. Nonetheless, when divided into tertiles, MMP-3 and TIMP-1 levels in the highest tertile were positively associated with the presence of carotid artery lesions (odds ratios=3.4 and 2.0, confidence intervals 1.7-13.9 and 1.3-7.9, respectively). Thus, serum levels of MMP-3, -9 and TIMP-1 are significantly elevated in asymptomatic hyperlipidemic subjects at high cardiovascular risk; however, MMP-3 and TIMP-1 levels are strongly positively associated with the presence of carotid lesions. Such elevations might reflect enhanced vascular matrix remodeling, a key feature of the progression of atherosclerotic disease.
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PMID:Serum matrix metalloproteinase-3 and tissue inhibitor of metalloproteinases-1 as potential markers of carotid atherosclerosis in infraclinical hyperlipidemia. 1286 Feb 60