Home About us Contact
|
Home About us Contact | ||
|
|
||
Inhibitory Ability (inhibitory + ability)
Selected AbstractsInhibition of ,-synuclein fibrillization by dopamine analogs via reaction with the amino groups of ,-synucleinFEBS JOURNAL, Issue 14 2005Implication for dopaminergic neurodegeneration Fibrillization of ,-synuclein (,-Syn) is closely associated with the formation of Lewy bodies in neurons and dopamine (DA) is a potent inhibitor for the process, which is implicated in the causative pathogenesis of Parkinson's disease (PD). To elucidate any molecular mechanism that may have biological relevance, we tested the inhibitory abilities of DA and several analogs including chemically synthetic and natural polyphenols in vitro. The MS and NMR characterizations strongly demonstrate that DA and its analogs inhibit ,-Syn fibrillization by a mechanism where the oxidation products (quinones) of DA analogs react with the amino groups of ,-Syn chain, generating ,-Syn,quinone adducts. It is likely that the amino groups of ,-Syn undergo nucleophilic attack on the quinone moiety of DA analogs to form imino bonds. The covalently cross-linked ,-Syn adducts by DA are primarily large molecular mass oligomers, while those by catechol and p -benzoquinone (or hydroquinone) are largely monomers or dimers. The DA quinoprotein retains the same cytotoxicity as the intact ,-Syn, suggesting that the oligomeric intermediates are the major elements that are toxic to the neuronal cells. This finding implies that the reaction of ,-Syn with DA is relevant to the selective dopaminergic loss in PD. [source] A decreased positivity for CD90 on human mesenchymal stromal cells (MSCs) is associated with a loss of immunosuppressive activity by MSCs,CYTOMETRY, Issue 3 2009Diana Campioni Abstract Biologic and clinical interest in human mesenchymal stromal cells (hMSC) has risen over the last years, mainly due to their immunosuppressive properties. In this study, we investigated the basis of immunomodulant possible variability using hMSC from different sources (amniotic membrane, chorion, and bone marrow from either healthy subjects or patients with hematological malignancies, HM) and having discordant positivity for several immunological markers. The CD90+ hMSC reduced lymphoproliferative response in phytohemagglutinin (PHA) activated peripheral blood mononuclear cells (PBMC) via sHLA-G and IL-10 up-modulation. On the contrary, hMSC showing a significantly lower expression for CD90 antigen, elicited a lymphoproliferative allogeneic response in PHA/PBMCs without any increase in soluble HLA-G and IL-10 levels. These data seems to suggest that CD90 molecule may be considered a novel predictive marker for hMSC inhibitory ability, and might cooperate with HLA-G molecule in regulating suppressive versus stimulatory properties of hMSC. These results may have clinical implication in either transplantation or in regenerative medicine fields. © 2008 Clinical Cytometry Society [source] Characterization and gene cloning of a novel serine protease with nematicidal activity from Trichoderma pseudokoningii SMF2FEMS MICROBIOLOGY LETTERS, Issue 2 2009Lei-Lei Chen Abstract Trichoderma pseudokoningii SMF2 is a biocontrol fungus with inhibitory ability against phytopathogenic fungi. Here, a crude extract of strain SMF2 in a solid ferment exhibited strong nematicidal activity against Meloidogyne incognita, and a novel serine protease SprT with nematicidal activity was purified from the crude extract. Protease SprT has a molecular mass of 31 kDa, a pH optimum of 8.5, and a temperature optimum of 60,65 °C. It had good thermostability, and was stable in an alkaline environment. SprT could degrade bovine serum albumin, lysozyme, and gelatin, and its activity was enhanced by many metal ions. The cuticles of nematodes treated by protease SprT obviously crimpled. Purified protease SprT could kill juveniles of M. incognita and inhibit egg hatch, suggesting that it is involved in the nematicidal process of T. pseudokoningii SMF2. The full-length cDNA gene-encoding protease SprT was cloned by rapid amplification of cDNA ends. Sequence analysis showed that SprT is a monodomain subtilase containing 284 amino acid residues. It had higher identities and a closer relation to the nematicidal serine proteases (59,69%) from nematode parasitic fungi than to the serine proteases (<50%) from Trichoderma. Protease SprT represents the first well-characterized subtilase with nematicidal activity from Trichoderma. [source] On the binding mode of urease active site inhibitors: A density functional studyINTERNATIONAL JOURNAL OF QUANTUM CHEMISTRY, Issue 11 2008M. Leopoldini Abstract The way with which boric acid, a rapid reversible competitive inhibitor, binds the urease active site was explored at density functional B3LYP level of theory. The catalytic core of the enzyme was simulated by two models of different size. In both cases, amino acid residues belonging to the inner and to the outer coordination spheres of nickel ions were replaced by smaller molecular species. Contrary to the experimental indication that attributes the inhibitory ability of this acid to the lack of a nucleophilic attack by the enzyme to the boron atom, we instead found that another possibility exists based on the presence of a strong covalent , bond between boron and urease that we think can be hardly broken to allow any course of the reaction. © 2008 Wiley Periodicals, Inc. Int J Quantum Chem, 2008 [source] Intravenous administration of melatonin reduces the intracerebral cellular inflammatory response following transient focal cerebral ischemia in ratsJOURNAL OF PINEAL RESEARCH, Issue 3 2007Ming-Yang Lee Abstract:, We have previously shown that exogenous melatonin improves the preservation of the blood,brain barrier (BBB) and neurovascular unit following cerebral ischemia,reperfusion. Recent evidence indicates that postischemic microglial activation exaggerates the damage to the BBB. Herein, we explored whether melatonin mitigates the cellular inflammatory response after transient focal cerebral ischemia for 90 min in rats. Melatonin (5 mg/kg) or vehicle was given intravenously at reperfusion onset. Immunohistochemistry and flow cytometric analysis were used to evaluate the cellular inflammatory response at 48 hr after reperfusion. Relative to controls, melatonin-treated animals did not have significantly changed systemic cellular inflammatory responses in the bloodstream (P > 0.05). Melatonin, however, significantly decreased the cellular inflammatory response by 41% (P < 0.001) in the ischemic hemisphere. Specifically, melatonin effectively decreased the extent of neutrophil emigration (Ly6G-positive/CD45-positive) and macrophage/activated microglial infiltration (CD11b-positive/CD45-positive) by 51% (P < 0.01) and 66% (P < 0.01), respectively, but did not significantly alter the population composition of T lymphocyte (CD3-positive/CD45-positive; P > 0.05). This melatonin-mediated decrease in the cellular inflammatory response was accompanied by both reduced brain infarction and improved neurobehavioral outcome by 43% (P < 0.001) and 50% (P < 0.001), respectively. Thus, intravenous administration of melatonin upon reperfusion effectively decreased the emigration of circulatory neutrophils and macrophages/monocytes into the injured brain and inhibited focal microglial activation following cerebral ischemia,reperfusion. The finding demonstrates melatonin's inhibitory ability against the cellular inflammatory response after cerebral ischemia,reperfusion, and further supports its pleuripotent neuroprotective actions suited either as a monotherapy or an add-on to the thrombolytic therapy for ischemic stroke patients. [source] Stimulatory and inhibitory epitopes in the T cell responses of mice to Der p 1CLINICAL & EXPERIMENTAL ALLERGY, Issue 6 2002A. G. Jarnicki Summary Background The responses of mice to the mite allergen Der p 1 have been used to study the mechanisms of allergic sensitization and the development of new types of immunotherapy. Many of the studies require a knowledge of the T cell epitopes, and because Der p 1 is polymorphic, the effect of natural amino acid substitution in the allergen. The intranasal administration of peptides containing T cell epitopes can induce a mucosal tolerance but it is not known if the major activity is limited to stimulatory peptides and if, as found for autoimmunity, some epitopes are not inhibitory. Objective To determine and compare the sequences of Der p 1 which contain stimulatory epitopes for the high responding H-2b and H-2q mice and the sequences which induce tolerance by intranasal administration of peptides. Methods T cell responses of mice immunized with Der p 1 were measured by in vitro T cell stimulation assays so an extensive study of epitope recognition and intranasal tolerance could be made. Synthetic peptides were used to examine the stimulatory and inhibitory ability of all Der p 1 sequences and to map the major H-2b epitope in detail. This included the effect of the common polymorphic amino acid 124 substitution found within this epitope. Results Three and two regions, respectively, were found to contain stimulatory T cell epitopes for H-2b and H-2q mice. The peptides in these regions were also the most active at inducing intranasal tolerance for the responding haplotype. The correspondence between inhibitory and stimulatory peptides was maintained for the fine mapping of the major H-2b epitope. This was found about a core region of 118,126 which was overlapping but separate to a consensus sequence for the binding of endogeneous peptides. Peptides with alanine at the naturally polymorphic residue 124 stimulated and inhibited responses to Der p 1 more effectively, while peptides with the valine 124 variant were immunogenic but poorly cross-reactive. Conclusions The intranasal administration of peptides representing each of five epitopes recognized by two strains of mice were able to induce mucosal tolerance and the major tolerizing activity was limited to these epitopes. The position of the core major epitope for C57 mice, which differs from a previously predicted epitope, and its specificity for the natural alanine 124 variant is described. [source] | |||||||||||||