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  • 1
    Electronic Resource
    Electronic Resource
    Springer
    Acta informatica 7 (1977), S. 357-360 
    ISSN: 1432-0525
    Source: Springer Online Journal Archives 1860-2000
    Topics: Computer Science
    Notes: Summary Hoare's axiomatic method is applied in order to describe two controversial features: side effects and general jumps. The relative simplicity of this description suggests that reasons for the exclusion of these features from programming languages are subtler than it has been thought.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Science Ltd
    Journal of neurochemistry 90 (2004), S. 0 
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Changes in mitochondrial integrity, reactive oxygen species release and Ca2+ handling are proposed to be involved in the pathogenesis of many neurological disorders including methylmalonic acidaemia and Huntington's disease, which exhibit partial mitochondrial respiratory inhibition. In this report, we studied the mechanisms by which the respiratory chain complex II inhibitors malonate, methylmalonate and 3-nitropropionate affect rat brain mitochondrial function and neuronal survival. All three compounds, at concentrations which inhibit respiration by 50%, induced mitochondrial inner membrane permeabilization when in the presence of micromolar Ca2+ concentrations. ADP, cyclosporin A and catalase prevented or delayed this effect, indicating it is mediated by reactive oxygen species and mitochondrial permeability transition (PT). PT induced by malonate was also present in mitochondria isolated from liver and kidney, but required more significant respiratory inhibition. In brain, PT promoted by complex II inhibition was stimulated by increasing Ca2+ cycling and absent when mitochondria were pre-loaded with Ca2+ or when Ca2+ uptake was prevented. In addition to isolated mitochondria, we determined the effect of methylmalonate on cultured PC12 cells and freshly prepared rat brain slices. Methylmalonate promoted cell death in striatal slices and PC12 cells, in a manner attenuated by cyclosporin A and bongkrekate, and unrelated to impairment of energy metabolism. We propose that under conditions in which mitochondrial complex II is partially inhibited in the CNS, neuronal cell death involves the induction of PT.
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Springer
    Bioscience reports 17 (1997), S. 43-52 
    ISSN: 1573-4935
    Keywords: Calcium ; cyclosporin A ; lipid peroxidation ; mitochondria ; mitochondrial membrane permeability transition ; protein oxidation ; reactive oxygen species
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology
    Notes: Abstract We have provided evidence that mitochondrial membrane permeability transition induced by inorganic phosphate, uncouplers or prooxidants such as t-butyl hydroperoxide and diamide is caused by a Ca2+-stimulated production of reactive oxygen species (ROS) by the respiratory chain, at the level of the coenzyme Q. The ROS attack to membrane protein thiols produces cross-linkage reactions, that may open membrane pores upon Ca2+ binding. Studies with submitochondrial particles have demonstrated that the binding of Ca2+ to these particles (possibly to cardiolipin) induces lipid lateral phase separation detected by electron paramagnetic resonance experiments exploying stearic acids spin labels. This condition leads to a disorganization of respiratory chain components, favoring ROS production and consequent protein and lipid oxidation.
    Type of Medium: Electronic Resource
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  • 4
    Electronic Resource
    Electronic Resource
    Springer
    Bioscience reports 19 (1999), S. 525-533 
    ISSN: 1573-4935
    Keywords: Mitochondrial permeability transition ; acid pH ; protein sulfhydryl oxidation ; calcium ; reactive oxygen species
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology
    Notes: Abstract Ca2+ and inorganic phosphate-induced mitochondrial swelling and membrane protein thiol oxidation, which are associated with mitochondrial permeability transition, are inhibited by progressively decreasing the incubation medium pH between 7.2 and 6.0. Nevertheless, the detection of mitochondrial H2O2 production under these conditions is increased. Permeability transition induced by phenylarsine oxide, which promotes membrane protein thiol cross-linkage in a process independent of Ca2+ or reactive oxygen species, is also strongly inhibited in acidic incubation media. In addition, we observed that the decreased protein thiol reactivity with phenylarsine oxide or phenylarsine oxide-induced swelling at pH 6.0 is reversed by diethyl pyrocarbonate, in a hydroxylamine-sensitive manner. These results provide evidence that the inhibition of mitrochondrial permeability transition observed at lower incubation medium pH is mediated by a decrease in membrane protein thiol reactivity, related to the protonation of protein histidyl residues.
    Type of Medium: Electronic Resource
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  • 5
    Electronic Resource
    Electronic Resource
    Springer
    ISSN: 1573-6881
    Keywords: Calcium ; cyclosporin A ; mitochondria ; mitochondrial permeability transition pore ; protein oxidation ; reactive oxygen species
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology , Physics
    Notes: Abstract We have previously shown that mitochondrial membrane potential (δψ) drop promoted by prooxidants and Ca2+ can be reversed but not sustained by ethylene glycol-bis(β-aminoethylether)-N,N,N′,N′-tetraacetic acid (EGTA) unless dithiothreitol (DTT), a disulfide reductant, is also added [Valle, V. G. R., Fagian, M. M., Parentoni, L. S., Meinicke, A. R., and Vercesi, A. E. (1993).Arch. Biochem. Biophys. 307, 1–7]. In this study we show that catalase or ADP are also able to potentiate this EGTA effect. When EGTA is added long after (12 min) the completion of swelling or δψ elimination, no membrane resealing occurs unless the EGTA addition was preceded by the inclusion of DTT, ADP, or catalase soon after δψ was collapsed. Total δψ recovery by EGTA is obtained only in the presence of ADP. The sensitivity of the ADP effect to carboxyatractyloside strongly supports the involvement of the ADP/ATP carrier in this mechanism. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis of solubilized membrane proteins shows that protein aggregation due to thiol cross-linkage formed during δψ drop continues even after δψ is already eliminated. Titration with 5,5′-dithio-bis(2-nitrobenzoic acid) supports the data indicating that the formation of protein aggregates is paralleled by a decrease in the content of membrane protein thiols. Since the presence of ADP and EGTA prevents the progress of protein aggregation, we conclude that this process is responsible for both increased permeability to larger molecules and the irreversibility of δΩ drop. The protective effect of catalase suggests that the continuous production of protein thiol cross-linking is mediated by mitochondrial generated reactive oxygen species.
    Type of Medium: Electronic Resource
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  • 6
    Electronic Resource
    Electronic Resource
    Springer
    ISSN: 1573-6881
    Keywords: Mitochondria ; triarylmethane dyes ; photodynamic therapy ; respiration ; mitochondrial permeability transition ; cyclosporin A ; calcium ; proton transport
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology , Physics
    Notes: Abstract The mitochondrial effects of submicromolar concentrations of six triarylmethane dyes, withpotential applications in antioncotic photodynamic therapy, were studied. All dyes promotedan inhibition of glutamate or succinate-supported respiration in uncoupled mitochondria, in amanner stimulated photodynamically. No inhibition of N,N,N′,N′-tetramethyl-p-phenylenediamine(TMPD) supported respiration was observed, indicating that these dyes do not affectmitochondrial complex IV. When mitochondria were energized with TMPD in the absence ofan uncoupler, treatment with victoria blue R, B, or BO, promoted a dissipation of mitochondrialmembrane potential and increase of respiratory rates, compatible with mitochondrialuncoupling. This effect was observed even in the dark, and was not prevented by EGTA, Mg2+ orcyclosporin A, suggesting that it is promoted by a direct effect of the dye on inner mitochondrialmembrane permeability to protons. Indeed, victoria blue R, B, and BO promoted swellingof valinomycin-treated mitochondria incubated in a hyposmotic K+-acetate-based medium,confirming that these dyes act as classic protonophores such as FCCP. On the other hand, ethylviolet, crystal violet, and malachite green promoted a dissipation of mitochondrial membranepotential, accompanied by mitochondrial swelling, which was prevented by EGTA, Mg2+, andcyclosporin A, demonstrating that these drugs induce mitochondrial permeability transition.This mitochondrial permeabilization was followed by respiratory inhibition, attributable tocytochrome c release, and was caused by the oxidation of NAD(P)H promoted by these drugs.
    Type of Medium: Electronic Resource
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