Charging nanoparticles: increased binding of Gd@C82(OH)22 derivatives to human MMP-9

Nanoscale ◽  
2018 ◽  
Vol 10 (12) ◽  
pp. 5667-5677 ◽  
Author(s):  
Serena H. Chen ◽  
Seung-gu Kang ◽  
Judong Luo ◽  
Ruhong Zhou
Keyword(s):  
Matrix Metalloproteinase ◽  
Ligand Specificity ◽  
Mmp Inhibitors ◽  
Catalytic Zinc ◽  
Zinc Site

Unlike most matrix metalloproteinase (MMP) inhibitors, which target the conserved catalytic zinc site, Gd@C82(OH)22 indirectly inhibits MMP-9 activity by binding at the ligand specificity S1′ loop.

scholarly journals Recent insights into natural product inhibitors of matrix metalloproteinases

MedChemComm ◽  
2019 ◽  
Vol 10 (12) ◽  
pp. 2024-2037 ◽  
Author(s):  
Geetha B. Kumar ◽  
Bipin G. Nair ◽  
J. Jefferson P. Perry ◽  
David B. C. Martin
Keyword(s):  
Cardiovascular Disease ◽  
Matrix Metalloproteinases ◽  
Matrix Metalloproteinase ◽  
Natural Product ◽  
Human Health ◽  
Neurodegenerative Disorders ◽  
Biological Functions ◽  
Mmp Inhibitors ◽  
The Matrix ◽  
Health And Disease

Members of the matrix metalloproteinase (MMP) family have biological functions that are central to human health and disease, and MMP inhibitors have been investigated for the treatment of cardiovascular disease, cancer and neurodegenerative disorders.

A novel hydra matrix metalloproteinase (HMMP) functions in extracellular matrix degradation, morphogenesis and the maintenance of differentiated cells in the foot process

Development ◽  
2000 ◽  
Vol 127 (4) ◽  
pp. 907-920 ◽  
Author(s):  
A.A. Leontovich ◽  
J. Zhang ◽  
K. Shimokawa ◽  
H. Nagase ◽  
M.P. Sarras
Keyword(s):  
Extracellular Matrix ◽  
Matrix Metalloproteinase ◽  
Longitudinal Axis ◽  
The Body ◽  
Mmp Inhibitors ◽  
Functional Studies ◽  
Cell Transdifferentiation ◽  
Basal Disk ◽  
Foot Process ◽  
Hemopexin Domain

As a member of Cnidaria, the body wall of hydra is structurally reduced to an epithelial bilayer with an intervening extracellular matrix (ECM). Biochemical and cloning studies have shown that the molecular composition of hydra ECM is similar to that seen in vertebrates and functional studies have demonstrated that cell-ECM interactions are important to developmental processes in hydra. Because vertebrate matrix metalloproteinases (MMPs) have been shown to have an important role in cell-ECM interactions, the current study was designed to determine whether hydra has homologues of these proteinases and, if so, what function these enzymes have in morphogenesis and cell differentiation in this simple metazoan. Utilizing a PCR approach, a single hydra matrix metalloproteinase, named HMMP was identified and cloned. The structure of HMMP was similar to that of vertebrate MMPs with an overall identity of about 35%. Detailed structural analysis indicated some unique features in (1) the cysteine-switch region of the prodomain, (2) the hinge region preceding the hemopexin domain, and (3) the hemopexin domain. Using a bacterial system, HMMP protein was expressed and folded to obtain an active enzyme. Substrate analysis studies indicated that recombinant HMMP could digest a number of hydra ECM components such as hydra laminin. Using a fluorogenic MMP substrate assay, it was determined that HMMP was inhibited by peptidyl hydroxamate MMP inhibitors, GM6001 and matlistatin, and by human recombinant TIMP-1. Whole-mount in situ studies indicated that HMMP mRNA was expressed in the endoderm along the entire longitudinal axis of hydra, but at relatively high levels at regions where cell-transdifferentiation occurred (apical and basal poles). Functional studies using GM6001 and TIMP-1 indicated that these MMP inhibitors could reversibly block foot regeneration. Blockage of foot regeneration was also observed using antisense thio-oligo nucleotides to HMMP introduced into the endoderm of the basal pole using a localized electroporation technique. Studies with adult intact hydra found that GM6001 could also cause the reversible de-differentiation or inhibition of transdifferentiation of basal disk cells of the foot process. Basal disk cells are adjacent to those endoderm cells of the foot process that express high levels of HMMP mRNA. In summary, these studies indicate that hydra has at least one MMP that is functionally tied to morphogenesis and cell transdifferentiation in this simple metazoan.

scholarly journals Matrix Metalloproteinase Inhibition in a Murine Model of Cavitary Tuberculosis Paradoxically Worsens Pathology

2018 ◽  
Vol 219 (4) ◽  
pp. 633-636 ◽  
Author(s):  
Alvaro A Ordonez ◽  
Supriya Pokkali ◽  
Julian Sanchez-Bautista ◽  
Mariah H Klunk ◽  
Michael E Urbanowski ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Mycobacterium Tuberculosis ◽  
Matrix Metalloproteinases ◽  
Pulmonary Tuberculosis ◽  
Matrix Metalloproteinase ◽  
Murine Model ◽  
Potent Inhibitor ◽  
Mmp Inhibitors

Abstract Matrix metalloproteinases (MMPs) degrade extracellular matrix and are implicated in tuberculosis pathogenesis and cavitation. In particular, MMP-7 is induced by hypoxia and highly expressed around pulmonary cavities of Mycobacterium tuberculosis–infected C3HeB/FeJ mice. In this study, we evaluated whether administration of cipemastat, an orally available potent inhibitor of MMP-7, could reduce pulmonary cavitation in M. tuberculosis–infected C3HeB/FeJ mice. We demonstrate that, compared with untreated controls, cipemastat treatment paradoxically increases the frequency of cavitation (32% vs 7%; P = .029), immunopathology, and mortality. Further studies are needed to understand the role of MMP inhibitors as adjunctive treatments for pulmonary tuberculosis.

Sign in / Sign up

Export Citation Format

Share Document