Activation and modulation of 72kDa matrix metalloproteinase-2 by peroxynitrite and glutathione

Viappiani, Serena; Nicolescu, Adrian C.; Holt, Andrew; Sawicki, Grzegorz; Crawford, Bryan D.; León, Hernando; Mulligen, Tyler van; Schulz, Richard

doi:10.1016/j.bcp.2008.11.004

Cited by 203 publications

(167 citation statements)

References 30 publications

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“…18 Several studies showed that MMP might be also regulated via non-proteolytic pathways through the post-translational modifications. 34 Peroxinitrite and GSH directly activate and modulate the MMP via a mechanism involving S-glutathiolation, 15 suggesting a relationship between redox status and MMP enzymes. Moreover, oxidative stress has been shown to regulate MMP through changes in their expression and direct interaction with Zn-thiol groups of catalytic site of latent MMP.…”

Section: Discussionmentioning

confidence: 99%

Relationship Between Myocardial Redox State and Matrix Metalloproteinase Activity in Patients on Left Ventricular Assist Device Support

Caruso

Caselli

Boroni

et al. 2011

Circ J

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Background: Redox aminothiols have been reported to modulate the activity of recombinant metalloproteinases (MMP). The aim of the present study was to investigate the effects of myocardial redox state on the activities of MMP-2 and -9 implicated in cardiac remodeling in end-stage heart failure patients supported by left ventricular assist device (LVAD). Methods and Results:During heart transplant (HT) surgery, myocardial specimens (MS) from right ventricular walls and LV walls were obtained from 7 LVAD recipients (LVAD group, MS n=35) and from 7 stable HT candidates on medical therapy (MT group, MS n=35). Myocardial MMP-2 and -9 activities and expression, tissue inhibitor of MMP (TIMP)-1 and -4, transforming growth factor (TGF)-β1 and aminothiol concentrations were measured. MMP-2 and -9 activities were evaluated also by incubating MS with different amounts of reduced and oxidized glutathione (GSH). MMP-2 and -9 activities and expression were lower in the LVAD group, whereas myocardial TIMP-1 and -4 concentrations were comparable to those of MT patients. Higher GSH and TGF-β1 concentrations were found in LVAD-recipients. Only GSH concentrations were inversely related to MMP-2 and -9 activities. In vitro, GSH had an inhibitory effect on MMP-2 and -9 activities.Conclusions: LVAD recipients show reduced myocardial MMP-2 and -9 activities and expression when compared to medically treated patients. Changes of myocardial redox state, predominantly GSH-dependent, appear to modulate MMP-2 and -9 activities by an inhibitory effect dependent on thiol content. These data support a role of GSH cycle in modulating the extracellular matrix in end-stage heart failure patients supported by LVAD. (Circ J 2011; 75: 2387 - 2396

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Section: Discussionmentioning

confidence: 99%

Relationship Between Myocardial Redox State and Matrix Metalloproteinase Activity in Patients on Left Ventricular Assist Device Support

Caruso

Caselli

Boroni

et al. 2011

Circ J

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“…Transcription of many MMPs genes is inducible: the enhancers of MMPs genes transcription include growth factors, cytokines, chemical agents, physical stresses, oncogenic cellular transformation, etc…, while suppressive factors are Transforming Growth Factor-b (TGF-b), retinoic acids and glucocorticoids (Nagase and Woessner 1999;Han et al 2008;Jackson et al 2009;Viappiani et al 2009). All MMPs are synthesized as pre-pro-enzyme and secreted as pro-enzyme (inactive form).…”

Section: Introductionmentioning

confidence: 99%

“…All MMPs are synthesized as pre-pro-enzyme and secreted as pro-enzyme (inactive form). Activation is extracellular and requires the disruption of the ''cysteine switch'' and the removal of the pro-peptide (Nagase and Woessner 1999;Viappiani et al 2009). …”

Section: Introductionmentioning

confidence: 99%

Immunohistochemical and transcriptional expression of matrix metalloproteinases in full-term human umbilical cord and Human Umbilical Vein Endothelial Cells

2010

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Matrix metalloproteinases (MMPs) are extracellular zinc-dependent endopeptidases involved in the degradation and remodelling of extracellular matrix in physiological and pathological processes. MMPs also have a role on cell proliferation, migration, differentiation, angiogenesis and apoptosis. Umbilical cord is a special organ subjected to many changes during pre-natal life and whose cells can maintain a certain degree of plasticity also in post-natal period; for example recently they have been used as a source of stem cells. In this work we investigated the expression of MMPs in human umbilical cord and Human Umbilical Vein Endothelial Cells (HUVEC) though immunohistochemistry, RT-PCR and gelatin zymography. MMP-2 protein is expressed in the amniotic epithelium of human umbilical cord and in few sub-epithelial fibroblasts, while MMP-3 and MMP-10 only in the umbilical epithelium. MMP-8, MMP-9 and MMP-13 immunoreactivity is localised in the epithelium and in Wharton's jelly mesenchymal cells. Immunocytochemistry also revealed protein expression for MMP-2, 3, 8, 9 and 10 in cultured HUVEC. In agreement with immunohistochemical data, RT-PCR analysis performed on samples of whole umbilical cord confirmed the transcriptional expression for the genes encoding all the six matrix metalloproteinases investigated, while in HUVEC only the expression of MMP-2, 3, 9, 10 and 13 mRNAs was detected. Gelatin zymograpgy showed a clear MMP-2 and MMP-9 enzymatic activity in the conditioned medium of HUVEC at different culture passages, suggesting that HUVEC secrete gelatinases, that afterwards undergo extracellular activation, and this ability is not affected by passage number.

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“…Here we have described the role of nitrosylation, nitration and phosphorylation of cardiac contractile proteins, as substrates for enzymatic reaction, in models of oxidative stress which result in their increased degradation by a proteolytic enzyme (MMP-2) both in vitro and in vivo (Figure 2). It has been described that posttranslational modification of MMP-2 triggered by oxidative stress can activate the enzyme (Viappiani et al 2009). Although this may be the case in the in vivo and ex vivo models, the same observations were made in in vitro experiments in which MMP-2 is not posttranslational modified.…”

Section: Resultsmentioning

confidence: 99%

Posttranslational Modifications of Myosin Light Chains Determine the Protein Fate

Cadete¹,

Sawicki²

2012

Proteomics - Human Diseases and Protein Functions

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Activation and modulation of 72kDa matrix metalloproteinase-2 by peroxynitrite and glutathione

Cited by 203 publications

References 30 publications

Relationship Between Myocardial Redox State and Matrix Metalloproteinase Activity in Patients on Left Ventricular Assist Device Support

Relationship Between Myocardial Redox State and Matrix Metalloproteinase Activity in Patients on Left Ventricular Assist Device Support

Immunohistochemical and transcriptional expression of matrix metalloproteinases in full-term human umbilical cord and Human Umbilical Vein Endothelial Cells

Posttranslational Modifications of Myosin Light Chains Determine the Protein Fate

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