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71.
Hydrogen peroxide inhibits caspase-dependent apoptosis by inactivating procaspase-9 in an iron-dependent manner 总被引:5,自引:0,他引:5
Barbouti A Amorgianiotis C Kolettas E Kanavaros P Galaris D 《Free radical biology & medicine》2007,43(10):1377-1387
Apoptosis represents a physiological form of cell death, the perturbation of which may contribute to the development of several diseases connected with accumulation of unwanted cells or excessive cell loss. We have previously shown that the continuous presence of low concentrations of H2O2 (generated by the action of glucose oxidase) was able to inhibit caspase-mediated apoptosis in Jurkat cells. The main purpose of the present study was to elucidate the exact molecular mechanism(s) underlying this inhibitory action of H2O2. The results presented show that events like outer mitochondrial membrane permeabilization, release of cytochrome c from mitochondria, oligomerization of Apaf-1, and recruitment of procaspase-9 to apoptosomes were taking place normally, but further advancement toward activation of the execution caspases was interrupted when H2O2 was present during the apoptotic process. From the results presented in this work, it emerges that the inhibition of procaspase-9 autoactivation was probably due to the reversible oxidation of sensitive cysteine residues in this molecule. Remarkably, caspase-9 activation and the ensuing caspase cascade proceeded normally in the presence of H2O2 under conditions of iron deprivation, indicating that the inhibition of procaspase-9 activation was an iron-dependent process. Collectively, these results highlighted the potential role of available intracellular iron ions in signaling mechanisms related to apoptotic cell death. 相似文献
72.
Baskal Svetlana Beckmann Bibiana Stahmer Laura Peter Corinna Bohnhorst Bettina Das Anibh Martin Tsikas Dimitrios 《Amino acids》2022,54(12):1611-1619
Amino Acids - We measured free and proteinic concentrations of native and modified amino acids from post-translational modifications (PTMs) and correlated them with the activity of SIRT1 and SIRT3... 相似文献
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76.
Reed E S Harrison Ronald D Gorham Dimitrios Morikis 《Protein science : a publication of the Protein Society》2015,24(5):789-802
As a part of innate immunity, the complement system relies on activation of the alternative pathway (AP). While feed-forward amplification generates an immune response towards foreign surfaces, the process requires regulation to prevent an immune response on the surface of host cells. Factor H (FH) is a complement protein secreted by native cells to negatively regulate the AP. In terms of structure, FH is composed of 20 complement-control protein (CCP) modules that are structurally homologous but vary in composition and function. Mutations in these CCPs have been linked to states of autoimmunity. In particular, several mutations in CCP 19-20 are correlated to atypical hemolytic uremic syndrome (aHUS). From crystallographic structures there are three putative binding sites of CCP 19-20 on C3d. Since there has been some controversy over the primary mode of binding from experimental studies, we approach characterization of binding using computational methods. Specifically, we compare each binding mode in terms of electrostatic character, structural stability, dissociative and associative properties, and predicted free energy of binding. After a detailed investigation, we found two of the three binding sites to be similarly stable while varying in the number of contacts to C3d and in the energetic barrier to complex dissociation. These sites are likely physiologically relevant and may facilitate multivalent binding of FH CCP 19-20 to C3b and either C3d or host glycosaminoglycans. We propose thermodynamically stable binding with modules 19 and 20, the latter driven by electrostatics, acting synergistically to increase the apparent affinity of FH for host surfaces. 相似文献
77.
Dimitrios Tsiantoulas Thomas Perkmann Taras Afonyushkin Andreas Mangold Thomas A. Prohaska Nikolina Papac-Milicevic Vincent Millischer Caroline Bartel Sohvi H?rkk? Chantal M. Boulanger Sotirios Tsimikas Michael B. Fischer Joseph L. Witztum Irene M. Lang Christoph J. Binder 《Journal of lipid research》2015,56(2):440-448
Oxidation-specific epitopes (OSEs) present on apoptotic cells and oxidized low density lipoprotein (OxLDL) represent danger-associated molecular patterns that are recognized by different arcs of innate immunity, including natural IgM antibodies. Here, we investigated whether circulating microparticles (MPs), which are small membrane vesicles released by apoptotic or activated cells, are physiological carriers of OSEs. OSEs on circulating MPs isolated from healthy donors and patients with ST-segment elevation myocardial infarction (STE-MI) were characterized by flow cytometry using a panel of OSE-specific monoclonal antibodies. We found that a subset of MPs carry OSEs on their surface, predominantly malondialdehyde (MDA) epitopes. Consistent with this, a majority of IgM antibodies bound on the surface of circulating MPs were found to have specificity for MDA-modified LDL. Moreover, we show that MPs can stimulate THP-1 (human acute monocytic leukemia cell line) and human primary monocytes to produce interleukin 8, which can be inhibited by a monoclonal IgM with specificity for MDA epitopes. Finally, we show that MDA+ MPs are elevated at the culprit lesion site of patients with STE-MI. Our results identify a subset of OSE+ MPs that are bound by OxLDL-specific IgM. These findings demonstrate a novel mechanism by which anti-OxLDL IgM antibodies could mediate protective functions in CVD. 相似文献
78.
Irene Friligou Evangelia Papadimitriou Dimitrios Gatos John Matsoukas Theodore Tselios 《Amino acids》2011,40(5):1431-1440
A fast and efficient microwave-assisted solid phase peptide synthesis (MW-SPPS) of a 51mer peptide, the main heparin-binding
site (60–110) of human pleiotrophin (hPTN), using 2-chlorotrityl chloride resin (CLTR-Cl) following the 9-fluorenylmethyloxycarbonyl/tert-butyl (Fmoc/tBu) methodology and with the standard N,N′-diisopropylcarbodiimide/1-hydroxybenzotriazole (DIC/HOBt) coupling reagents, is described. An MW-SPPS protocol was for the
first time successfully applied to the acid labile CLTR-Cl for the faster synthesis of long peptides (51mer peptide) and with
an enhanced purity in comparison to conventional SPPS protocols. The synthesis of such long peptides is not trivial and it
is generally achieved by recombinant techniques. The desired linear peptide was obtained in only 30 h of total processing
time and in 51% crude yield, in which 60% was the purified product obtained with 99.4% purity. The synthesized peptide was
purified by reversed phase high performance liquid chromatography (RP-HPLC) and identified by electrospray ionization mass
spectrometry (ESI-MS). Then, the regioselective formation of the two disulfide bridges of hPTN 60–110 was successfully achieved
by a two-step procedure, involving an oxidative folding step in dimethylsulfoxide (DMSO) to form the Cys77–Cys109 bond, followed by iodine oxidation to form the Cys67–Cys99 bond. 相似文献
79.
Despite the numerous compost stability and maturity tests, no universally accepted compost stability or maturity index exists. The fluorescein di-acetate (FDA) enzymatic assay, originating from soil studies, is examined here as a potential new compost stability test, and is compared to microbial respiration and phytotoxicity indices. Thirteen composts were used in the study from different source materials. Static microbial respiration activity indices calculated were the cumulative O2 consumptions, O2 consumption rates, total C-CO2 production, the respiratory quotient and the bio C/N ratio. Compost phytotoxicity was quantified via a 7-day tomato seed germination assay. Results showed that the net fluorescein release rates correlated with all stability indices. The germination index marginally correlated with the fluorescein release rates, but not with any of the other stability indices. New limits to classify composts regarding their stability were proposed. 相似文献
80.
Michael MichailidesGerasimos Christou Christos S. AkratosAthanasia G. Tekerlekopoulou Dimitrios V. Vayenas 《International biodeterioration & biodegradation》2011,65(3):560-564
The composting of olive leaves and olive pomace from a three-phase olive mill was tested as a method for solid waste reuse. The process was carried out using a compost windrow and mixing olive leaves and pomace at a ratio of 1:2. Compost was retained in the windrow for 60 days during which thermophilic temperatures developed for the first 40 days. The compost was then placed into a closed area to mature for another 60 days. The final product proved to be high quality amendment with C/N 27.1 and high nutrient concentrations (N, 1.79%; P, 0.17%; K, 4.97%; Na, 2.8%). Mature compost presented the highest germination index (198%) reported to date, as the germination index in the majority of previous studies is under 80%. Furthermore, tests revealed that addition of 31.5 tons of compost per ha, could increase lettuce yield by 145%. 相似文献