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Cathepsin B Inhibitor (cathepsin + b_inhibitor)
Selected AbstractsNeurovascular and neuronal protection by E64d after focal cerebral ischemia in ratsJOURNAL OF NEUROSCIENCE RESEARCH, Issue 4 2006Tamiji Tsubokawa Abstract Calpains and cathepsins are two families of proteases that play an important role in ischemic cell death. In this study, we investigated the effect of E64d, a ,-calpain and cathepsin B inhibitor, in the prevention of neuronal and endothelial apoptotic cell death after focal cerebral ischemia in rats. Rats underwent 2 hr of transient focal ischemia from middle cerebral artery occlusion (MCAO) and were sacrificed 24 hr later. E64d (5 mg/ kg intraperitoneally) was administered 30 min before MCAO. Assessment included neurological function, infarction volume, brain water content, blood,brain barrier permeability, histology, and immunohistochemistry. The E64d-treated rats had significant brain protection against ischemic damage. We observed a reduction of infarction volume, brain edema, and improved neurological scores in E64d-treated rats compared with the nontreated control. Furthermore, there was a remarkable reduction in both proteases and caspase-3 activation and apoptotic changes in both neurons and endothelial cells in E64d-treated rats. These results suggest that E64d protects the brain against ischemic/reperfusion injury by attenuating neuronal and endothelial apoptosis. © 2006 Wiley-Liss, Inc. [source] Zaire Ebola virus entry into human dendritic cells is insensitive to cathepsin L inhibitionCELLULAR MICROBIOLOGY, Issue 2 2010Osvaldo Martinez Summary Cathepsins B and L contribute to Ebola virus (EBOV) entry into Vero cells and mouse embryonic fibroblasts. However, the role of cathepsins in EBOV-infection of human dendritic cells (DCs), important targets of infection in vivo, remains undefined. Here, EBOV-like particles containing a ,-lactamase,VP40 fusion reporter and Ebola virus were used to demonstrate the cathepsin dependence of EBOV entry into human monocyte-derived DCs. However, while DC infection is blocked by cathepsin B inhibitor, it is insensitive to cathepsin L inhibitor. Furthermore, DCs pre-treated for 48 h with TNF, were generally less susceptible to entry and infection by EBOV. This decrease in infection was associated with a decrease in cathepsin B activity. Thus, cathepsin L plays a minimal, if any, role in EBOV infection in human DCs. The inflammatory cytokine TNF, modulates cathepsin B activity and affects EBOV entry into and infection of human DCs. [source] Biochemical characterization of human cathepsin X revealed that the enzyme is an exopeptidase, acting as carboxymonopeptidase or carboxydipeptidaseFEBS JOURNAL, Issue 17 2000Ivica Klemen Cathepsin X, purified to homogeneity from human liver, is a single chain glycoprotein with a molecular mass of ,,33 kDa and pI 5.1,5.3. Cathepsin X was inhibited by stefin A, cystatin C and chicken cystatin (Ki = 1.7,15.0 nm), but poorly or not at all by stefin B (Ki > 250 nm) and l -kininogen, respectively. The enzyme was also inhibited by two specific synthetic cathepsin B inhibitors, CA-074 and GFG-semicarbazone. Cathepsin X was similar to cathepsin B and found to be a carboxypeptidase with preference for a positively charged Arg in P1 position. Contrary to the preference of cathepsin B, cathepsin X normally acts as a carboxymonopeptidase. However, the preference for Arg in the P1 position is so strong that cathepsin X cleaves substrates with Arg in antepenultimate position, acting also as a carboxydipeptidase. A large hydrophobic residue such as Trp is preferred in the P1, position, although the enzyme cleaved all P1, residues investigated (Trp, Phe, Ala, Arg, Pro). Cathepsin X also cleaved substrates with amide-blocked C-terminal carboxyl group with rates similar to those of the unblocked substrates. In contrast, no endopeptidase activity of cathepsin X could be detected on a series of o -aminobenzoic acid-peptidyl- N -[2,-dinitrophenyl]ethylenediamine substrates. Furthermore, the standard cysteine protease methylcoumarine amide substrates (kcat/Km,,5.0 × 103 m,1·s,1) were degraded ,,25-fold less efficiently than the carboxypeptidase substrates (kcat/Km , 120.0 × 103 m,1·s,1). [source] Cathepsin B Inhibitory Tetraene Lactones from the Fungus Talaromyces wortmanniiHELVETICA CHIMICA ACTA, Issue 3 2009Yuesheng Dong Abstract Wortmannilactones E,H (1,4), four new cathepsin B inhibitors, were produced and isolated from the culture of the soil filamentous fungus Talaromyces wortmannii. Their structures and relative configurations were elucidated on the basis of 1D- and 2D-NMR techniques, three of them (1, 2, and 4) posses an oxabicyclo[2.2.1]heptane moiety. Compounds 1,4 showed inhibitory activities against cathepsin B with IC50 values of 4.3, 6.5, 13.0, and 6.0,,M, respectively. [source] | |||||||||||||