A rat carcinoma cell line (T2/H7) constitutively synthesised interstitial collagenase. When these cells were incubated with 12-O-tetradecanoylphorbol 13-acetate (TPA) they secreted an inhibitor of collagenase, which resulted in a net decrease of collagenolytic activity being detected in conditioned medium. Using reverse zymography, the Mr of the inhibitor was found to be 20,000 which suggests that it may be the rat homologue of inhibitor of metalloproteinase 2 (IMP2; TIMP-2), as it inhibited both the gelatinolytic and collagenolytic activities of rat collagenase. The inhibitor was separated from collagenase by filtration through a YM30 membrane. The inhibitor was purified further by sequential chromatography on heparin-Sepharose and Con A-Sepharose. It bound to heparin-Sepharose in 75 mM NaCl and was eluted with 300 mM NaCl. It did not bind to Con A-Sepharose, suggesting that it was a non-glycosylated molecule. The inhibitor was resistant to treatment with either trypsin, APMA or heat.
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http://dx.doi.org/10.1016/0304-4165(91)90189-n | DOI Listing |
In Silico Pharmacol
January 2025
College of Chemistry and Chemical Engineering, China University of Petroleum, Qingdao, 266580 China.
Matrix metalloproteinase-8 (MMP-8), a type II collagenase, is a key enzyme in the degradation of collagens and is implicated in various pathological processes, making it a promising target for drug discovery. Despite advancements in the development of MMP-8 inhibitors, concerns over potential adverse effects persist. This study aims to address these concerns by focusing on the development of novel compounds with improved safety profiles while maintaining efficacy.
View Article and Find Full Text PDFInt J Mol Sci
December 2024
Pittsburgh Heart, Lung and Blood Vascular Medicine Institute (VMI), University of Pittsburgh School of Medicine, Pittsburgh, PA 15260, USA.
Matrix metalloproteinase-2 (MMP-2), a zinc-dependent enzyme, plays a critical role in the degradation and remodeling of the extracellular matrix (ECM). As a member of the gelatinase subgroup of matrix metalloproteinases, MMP-2 is involved in a variety of physiological processes, including tissue repair, wound healing, angiogenesis, and embryogenesis. It is primarily responsible for the degradation of type IV and V collagen, fibronectin, laminin, and elastin, which are essential components of the ECM.
View Article and Find Full Text PDFBiomolecules
December 2024
Department of Orthopaedic Surgery, Kanazawa Medical University, Daigaku 1-1, Uchinada-machi, Kahoku-gun 920-0293, Japan.
Inflammation and oxidative stress are crucial for osteoarthritis (OA) pathogenesis. Despite the potential of pharmacological pretreatment of chondrocytes in preventing OA, its efficacy in preventing the progression of cartilage damage and promoting its recovery has not been examined. In this study, an HO-induced human OA-like chondrocyte cell model was created using H1467 primary human chondrocytes to evaluate the efficacy of interleukin (IL)-6 and cyclooxygenase (COX)-2 inhibitors (tocilizumab and celecoxib, respectively) in the prevention and treatment of cartilage damage.
View Article and Find Full Text PDFBiomolecules
November 2024
Laboratory of Molecular and Cell Biology, Istituto Dermopatico Dell'Immacolata (IDI-IRCCS), 00167 Rome, Italy.
UVB radiation induces DNA damage generating several thymine photo-adducts (TDPs), which can lead to mutations and cellular transformation. The DNA repair pathways preserve genomic stability by recognizing and removing photodamage. These DNA repair side products may affect cellular processes.
View Article and Find Full Text PDFJ Cereb Blood Flow Metab
January 2025
Neurovascular Research Unit, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, USA.
Rho-associated protein kinase (ROCK) inhibitors are therapeutic candidates in ischemic stroke and subarachnoid hemorrhage. However, their efficacy in intracerebral hemorrhage (ICH) is unknown. Here, we tested the efficacy of fasudil (10 mg/kg), an isoform-nonselective ROCK inhibitor, and NRL-1049 (10 mg/kg), a novel inhibitor with 43-fold higher selectivity for ROCK2 isoform compared with ROCK1, in a collagenase-induced ICH model in mice.
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