Effects of reactive metabolites of oxygen and nitrogen on gelatinase A activity

1997 ◽  
Vol 273 (2) ◽  
pp. L445-L450 ◽  
Author(s):  
M. W. Owens ◽  
S. A. Milligan ◽  
D. Jourd'heuil ◽  
M. B. Grisham
Keyword(s):  
Nitric Oxide ◽  
Matrix Protein ◽  
Gelatinase A ◽  
Simultaneous Generation ◽  
Zinc Thiolate ◽  
Switch Mechanism ◽  
Increased Activity ◽  
Metalloproteinase Activity ◽  
Cysteine Switch ◽  
Proper Balance

The regulation of matrix metalloproteinase activity is crucial for maintaining the proper balance of tissue remodeling vs. injury. Metalloproteinase proenzymes are activated when the active site zinc is exposed via a cysteine switch mechanism. Peroxynitrite, the product generated from the interaction between nitric oxide and superoxide, has been shown to release zinc from zinc-thiolate groups, suggesting that it might alter metalloproteinase activity. This study examined the effects of nitric oxide and superoxide generators on gelatinase A activity. Results showed that nitric oxide alone had no effect on gelatinase A activity relative to control, whereas superoxide-derived metabolites increased activity. The simultaneous generation of both nitric oxide and superoxide caused an inhibition of gelatinase A activity. This inhibition was reversed by the addition of hemoglobin, superoxide dismutase, or sodium urate, suggesting that peroxynitrite and/or peroxynitrous acid caused the inhibition. Authentic peroxynitrite also inhibited gelatinase A activity. We postulate that the relative fluxes of nitric oxide and superoxide at sites of inflammation may modulate metalloproteinase activity and thus affect matrix protein metabolism.

scholarly journals Myroilysin Is a New Bacterial Member of the M12A Family of Metzincin Metallopeptidases and Is Activated by a Cysteine Switch Mechanism

2017 ◽  
Vol 292 (13) ◽  
pp. 5195-5206 ◽  
Author(s):  
Dongqing Xu ◽  
Jiale Zhou ◽  
Xiangdi Lou ◽  
Jianhua He ◽  
Tingting Ran ◽  
...  
Keyword(s):  
Switch Mechanism ◽  
Cysteine Switch

scholarly journals Nitric Oxide Regulation of MMP-9 Activation and Its Relationship to Modifications of the Cysteine Switch†

Biochemistry ◽  
2008 ◽  
Vol 47 (21) ◽  
pp. 5832-5840 ◽  
Author(s):  
Sean M. McCarthy ◽  
Peter F. Bove ◽  
Dwight E. Matthews ◽  
Takaaki Akaike ◽  
Albert van der Vliet
Keyword(s):  
Nitric Oxide ◽  
Cysteine Switch

The Simultaneous Generation of Superoxide and Nitric Oxide Can Initiate Lipid Peroxidation in Human Low Density Lipoprotein

1992 ◽  
Vol 17 (1) ◽  
pp. 9-20 ◽  
Author(s):  
Victor M. Darley-usmar ◽  
Neil Hogg ◽  
Vanessa J. O'leary ◽  
Michael T. Wilson ◽  
Salvador Moncada
Keyword(s):  
Nitric Oxide ◽  
Lipid Peroxidation ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Low Density ◽  
Simultaneous Generation

scholarly journals The Coexpression of Reelin and Neuronal Nitric Oxide Synthase in a Subpopulation of Dentate Gyrus Neurons Is Downregulated in Heterozygous Reeler Mice

2010 ◽  
Vol 2010 ◽  
pp. 1-10 ◽  
Author(s):  
Raquel Romay-Tallón ◽  
Iria G. Dopeso-Reyes ◽  
April L. Lussier ◽  
Lisa E. Kalynchuk ◽  
Hector J. Caruncho
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
Dentate Gyrus ◽  
Matrix Protein ◽  
Molecular Layer ◽  
Neuronal Nitric Oxide Synthase ◽  
Stratum Radiatum ◽  
Extracellular Matrix Protein ◽  
Subgranular Zone ◽  
Oxide Synthase

Reelin is an extracellular matrix protein expressed in several interneuron subtypes in the hippocampus and dentate gyrus. Neuronal nitric oxide synthase (nNOS) is also expressed by interneurons in these areas. We investigated whether reelin and nNOS are co-localized in the same population of hippocampal interneurons, and whether this colocalization is altered in the heterozygous reeler mouse. We found colocalization of nNOS in reelin-positive cells in the CA1 stratum radiatum and lacunosum moleculare, the CA3 stratum radiatum, and the dentate gyrus subgranular zone, molecular layer, and hilus. In heterozygous reeler mice, the colocalization of nNOS in reelin-positive cells was significantly decreased only in the subgranular zone and molecular layer. The coexpression of reelin and nNOS in several hippocampal regions suggests that reelin and nNOS may work synergistically to promote glutamatergic function, and the loss of this coexpression in heterozygous reeler mice may underlie some of the behavioral deficits observed in these animals.

Amino-terminal TACE prodomain attenuates TNFR2 cleavage independently of the cysteine switch

2005 ◽  
Vol 288 (6) ◽  
pp. L1132-L1138 ◽  
Author(s):  
Caitriona A. Buckley ◽  
Farshid N. Rouhani ◽  
Maryann Kaler ◽  
Barbara Adamik ◽  
Feras I. Hawari ◽  
...  
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Inhibitory Activity ◽  
Catalytic Domain ◽  
Amino Terminus ◽  
Mucin Production ◽  
Inactive State ◽  
Amino Terminal ◽  
Switch Mechanism ◽  
Cysteine Switch

TNF-α-converting enzyme (TACE, ADAM17) cleaves membrane-associated cytokines and receptors and thereby regulates inflammatory and immune events, as well as lung development and mucin production. For example, the TACE-mediated cleavage of the type II 75-kDa TNF receptor (TNFR2) generates a soluble TNF-binding protein that modulates TNF bioactivity. TACE is synthesized as a latent proenzyme that is retained in an inactive state via an interaction between its prodomain and catalytic domain. Although the formation of an intramolecular bond between a cysteine in the prodomain and a zinc atom in the catalytic site had been thought to mediate this inhibitory activity, it was recently reported that the cysteine-switch motif is not required. Here, we hypothesized that the amino terminus of the TACE prodomain might contribute to the ability of the prodomain to maintain TACE in an inactive state independently of a cysteine-switch mechanism. We synthesized a 37-amino acid peptide corresponding to TACE amino acids 18–54 (N-TACE18–54) and assessed whether it possessed TACE inhibitory activity. In an in vitro model assay system, N-TACE18–54 attenuated TACE-catalyzed cleavage of a TNFR2:Fc substrate. Furthermore, N-TACE18–54 inhibited constitutive TNFR2 shedding from a human monocytic cell line by 42%. A 19-amino acid, leucine-rich domain, corresponding to TACE amino acids 30–48, demonstrated partial inhibitory activity. In summary, we have identified a subdomain within the amino terminus of the TACE prodomain that attenuates TACE catalytic activity independently of a cysteine-switch mechanism, which provides new insight into the regulation of TACE enzymatic activity.

scholarly journals Tadalafil Integrates Nitric Oxide-Hydrogen Sulfide Signaling to Inhibit High Glucose-induced Matrix Protein Synthesis in Podocytes

2015 ◽  
Vol 290 (19) ◽  
pp. 12014-12026 ◽  
Author(s):  
Hak Joo Lee ◽  
Denis Feliers ◽  
Meenalakshmi M. Mariappan ◽  
Kavithalakshmi Sataranatarajan ◽  
Goutam Ghosh Choudhury ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Protein Synthesis ◽  
Hydrogen Sulfide ◽  
High Glucose ◽  
Matrix Protein
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