bluuebunny/crossref_metadata_2025_split huggingface dataset:
Neuronal excitotoxicity: the role of mitochondria
Authors: Nicholls David G. , Budd Samantha L. 
Published: December 2008

AbstractChronic activation of NMDA receptors by glutamate is toxic to cultured neurons. The extensive Ca2+entry accompanying receptor activation is largely accumulated by the intracellular mitochondria, with resultant effects on mitochondrial membrane potential, ATP synthesis, glycolysis, reactive oxygen species generation and ultimately failure of cytoplasmic Ca2+homeostasis and cell death. Each of these parameters is inter‐related and in this review we describe attempts to separate out each factor to establish the sequence of events following NMDA receptor activation. The conclusion is that mitochondrial Ca2+accumulation is a key event in glutamate excitotoxicity, and that cells maintained by glycolysis in the absence of a mitochondrial membrane potential are highly resistant to glutamate excitotoxicity.
Selenophosphate as a substrate for mammalian selenocysteine synthase, its stability and toxicity
Authors: Mizutani Takaharu , Kanaya Kazuo , Tanabe Kazutaka 
Published: December 2008

AbstractThe mechanism of selenocysteine synthesis on tRNASec in mammals was previously studied by means of HSe− as a Se donor to synthesize selenocysteine. It has been recently established that HSe− in E. coli is activated by ATP to become selenophosphate (SeP). In this study, we provide evidence that [75Se]selenocysteine is produced by bovine selenocysteine synthase from Ser‐tRNASec and [75Se]SeP, synthesized from elemental 75Se and Tris(trimethylsilyl)phosphite. We also studied the stability of SeP by NMR measurement. SeP was stable during storage under nitrogen at ‐80°C for 3 months in 0.2 M Hepes buffer at pH 6.8. However, SeP decomposed at 0°C in air (half life 32 hrs) or at 22°C under nitrogen (half life 30 hrs) at pH 6.8. The half lives of SeP at ‐19°C in air and at 0°C under nitrogen at pH 6.8 were 740 and 840 hrs, respectively. At pH 4 under nitrogen at 22°C, the half life was 240 hrs. The half life was only 9.2 hrs at pH 9 under nitrogen at 0°C. Thus, SeP was proved to be stable at low temperature, under acidic and anaerobic conditions, but labile under neutral and alkaline conditions.The LD50 of SeP administered i.p. to mice was 37.5 mg/kg body weight.
ATP‐sensitive association of mortalin with the IL‐1 receptor type I
Authors: Sacht Gudrun , Brigelius‐Flohé Regina , Kiess Michael , Sztajer Helena , Flohé Leopold 
Published: December 2008

AbstractInterleukin‐1 (IL‐1) is a major proinflammatory cytokine mediating local and systemic responses of the immune system. Two types of IL‐1 receptors are known, but only the IL‐1 receptor type I initiates biological responses. Here we show that two proteins with nucleic acid binding potential and mortalin, a member of the HSP70‐family, are associated with the IL‐1 receptor type I irrespective of IL‐1 binding. The association of mortalin with the IL‐1 receptor type I is specifically reversed by ATP concentrations in the physiological range. Other nucleotides are not or much less effective. The in vitro dissociation of mortalin effects neither the receptor association nor the activity of IRAK, which initiates the IL‐1‐dependent phosphorylation cascade. The roles of the receptor‐associated proteins are therefore discussed in the context of receptor internalisation.
Structure and reaction mechanisms of multifunctional mitochondrial cytochrome bc1 complex
Authors: Yu Chang‐An , Zhang Li , Deng Kai‐Ping , Tian Hna , Xia Di , Kim Hoeon , Deisenhofer Johann , Yu Linda 
Published: December 2008

AbstractThe cytochrome bc1 complex from bovine heart mitochondria is a multi‐functional enzyme complex. In addition to electron and proton transfer activity, the complex also processes an activatable peptidase activity and a superoxide generating activity. The crystal structure of the complex exists as a closely interacting functional dimer. There are 13 transmembrane helices in each monomer, eight of which belong to cytochrome b, and five of which belong to cytochrome c1, Rieske iron‐sulfur protein (ISP), subunits 7, 10 and 11, one each. The distances of 21 Å between bL heme and bH heme and of 27 Å between bL heme and the iron‐sulfur cluster (FeS), accommodate well the observed fast electron transfers between the involved redox centers. However, the distance of 31 Å between heme c1 and FeS, makes it difficult to explain the high electron transfer rate between them. 3D structural analyses of the bc1 complexes co‐crystallized with the Qo site inhibitors suggest that the extramembrane domain of the ISP may undergo substantial movement during the catalytic cycle of the complex. This suggestion is further supported by the decreased in the cytochrome bc1 complex activity and the increased in activation energy for mutants with increased rigidity in the neck region of ISP.
Characterization ofSaccharomyces cerevisiaeubiquinone‐deficient mutants
Authors: Schultz Jeffery R. , Clarke Catherine F. 
Published: December 2008

AbstractUbiquinol (QH2) is a lipid‐soluble molecule that participates in cellular redox reactions. Previous studies have shown that yeast mutants lacking QH2are hypersensitive to treatment with polyunsaturated fatty acids (PUFAs) indicating that QH2can function as an antioxidant in vivo. In this study the effect of 1 mM linolenic acid on levels of Q6and Q6H2is assessed in both wild‐type and respiration‐deficient (atp2Δ) strains. The response of Q‐deficient mutants to other forms of oxidative stress is further characterized to define those conditions where QH2acts as an antioxidant. Endogenous antioxidant defense systems were also assessed in wild‐type, Q‐deficient, andatp2Δ strains. Superoxide dismutase (SOD) activity decreased and catalase activity increased in both Q‐deficient andatp2Δ mutants compared to wild‐type cells, suggesting that such changes result from the loss of respiration rather than the lack of Q.
Dynamics of antioxidant action of ubiquinol: A reappraisal
Authors: Shi Honglian , Noguchi Noriko , Niki Etsuo 
Published: December 2008

AbstractThe dynamics of action of ubiquinol as an antioxidant against lipid peroxidation was reinvestigated and compared with that ofα‐tocopherol. It was found that ubiquinol was 2.5 and 1.9 times more reactive thanα‐tocopherol toward phenoxyl and peroxyl radicals, respectively, at 25°C in ethanol and that it was capable of donating two hydrogen atoms toward oxygen radicals but that the apparent stoichiometric number decreased in the inhibition of lipid peroxidation, to even smaller than 1, due to its autoxidation. The autoxidation of ubiquinol proceeded even in the micelles and liposomal membranes in aqueous dispersions as well as in organic homogeneous solution. The apparent antioxidant activity of ubiquinol was smaller than that ofα‐tocopherol against lipid peroxidation in organic solution as judged from either rate of oxidation or duration of inhibition period. They exerted similar antioxidant potency against lipid peroxidation in the membranes and micelles in aqueous dispersions. The combination of ubiquinol andα‐tocopherol was suggested to be effective.
Protective role of ubiquinone in vitamin E and selenium‐deficient plasma membranes
Authors: Navarro Francisco , Arroyo Antonio , Martín Sergio F. , Bello Rosario I. , De Cabo Rafael , Burgess John R. , Navas Plácido , Villalba José M. 
Published: December 2008

AbstractWe have studied the effects of dietary depletion of vitamin E and selenium on endogenous ubiquinone‐dependent antioxidant system. Deficiency induced an increase in both coenzyme Q9 and Q10 in liver tissue, reaching a maximum between 4 and 7 weeks of deficient diet consumption. Cytochrome b5 reductase polypeptide was also enriched in membranes after 5 weeks of deficient diet consumption. Substantial DT‐diaphorase activity was found in deficient, but not in control plasma membranes. Deficient membranes were very sensitive to lipid peroxidation, although a great protection was observed after incubation with NAD(P)H. Our results show that liver cells can boost endogenous ubiquinone‐dependent protective mechanisms in response to deficiency in vitamin E and selenium.
Role of plasma membrane coenzyme Q on the regulation of apoptosis
Authors: López‐Lluch G. , Barroso M. P. , Martín S. F. , Fernández‐Ayala D. J. M. , Gómez‐Díaz C. , Villalba J. M. , Navas P. 
Published: December 2008

AbstractSerum withdrawal is a model to study the mechanisms involved in the induction of apoptosis caused by mild oxidative stress. Apoptosis induced by growth factors removal was prevented by the external addition of antioxidants such as ascorbate,α‐tocopherol and coenzyme Q (CoQ). CoQ is a lipophilic antioxidant which prevents oxidative stress and participates in the regeneration ofα‐tocopherol and ascorbate in the plasma membrane. We have found an inverse relationship between CoQ content in plasma membrane and lipid peroxidation rates in leukaemic cells. CoQ10 addition to serum‐free culture media prevented both lipid peroxidation and cell death. Also, CoQ10 addition decreased ceramide release after serum withdrawal by inhibition of magnesium‐dependent plasma membrane neutral‐sphingomyelinase. Moreover, CoQ10 addition partially blocked activation of CPP32/caspase‐3. These results suggest CoQ of the plasma membrane as a regulator of initiation phase of oxidative stress‐mediated serum withdrawal‐induced apoptosis.
Improved brain and muscle mitochondrial respiration with CoQ. An in vivo study by 31P‐MR spectroscopy in patients with mitochondrial cytopathies
Authors: Barbiroli Bruno , Iotti Stefano , Lodi Raffaele 
Published: December 2008

AbstractWe used in vivo phosphorus magnetic resonance spectroscopy (31P‐MRS) to study the effect of CoQ10 on the efficiency of brain and skeletal muscle mitochondrial respiration in ten patients with mitochondrial cytopathies. Before CoQ, brain [PCr] was remarkably lower in patients than in controls, while [Pi] and [ADP] were higher. Brain cytosolic free [Mg2+] and Δ G of ATP hydrolysis were also abnormal in all patients. MRS also revealed abnormal mitochondrial function in the skeletal muscles of all patients, as shown by a decreased rate of PCr recovery from exercise. After six‐months of treatment with CoQ (150 mg/day), all brain MRS‐measurable variables as well as the rate of muscle mitochondrial respiration were remarkably improved in all patients. These in vivo findings show that treatment with CoQ in patients with mitochondrial cytopathies improves mitochondrial respiration in both brain and skeletal muscles, and are consistent with Lenaz's view that increased CoQ concentration in the mitochondrial membrane increases the efficiency of oxidative phosphorylation independently of enzyme deficit.
CoQ10: Could it have a role in cancer management?
Authors: Hodges S. , Hertz N. , Lockwood K. , Lister R. 
Published: December 2008

AbstractCoenzyme Q10 or ubiquinone has been shown to have both anti‐cancer and immune system enhancing properties when tested in animals. Preliminary results reported here suggest that it might inhibit tumour‐associated cytokines. Clinical studies conducted with combination therapies of CoQ10 and other antioxidants are ongoing, but the results are difficult evaluate owing to the lack of proper control groups and of initial randomisation. Also on the basis of some anti‐cancer effects of antioxidants reported in literature, further animal studies and a proper clinical trial of coenzyme Q10 in cancer patients are needed.
Lycopene and β‐carotene decompose more rapidly than lutein and zeaxanthin upon exposure to various pro‐oxidants in vitro
Authors: Siems Werner G. , Sommerburg Olaf , Van Kuijk Frederik J.G.M. 
Published: December 2008

AbstractMajor carotenoids of human plasma and tissues were exposed to radical‐initiated autoxidation conditions. The consumption of lutein and zeaxanthin, the only carotenoids in the retina, and lycopene and β‐carotene, the most effective quenchers of singlet oxygen in plasma, were compared.Under all conditions of free radical‐initiated autoxidation of carotenoids which were investigated, the breakdown of lycopene and β‐carotene was much faster than that of lutein and zeaxanthin. Under the influence of UV light in presence of Rose Bengal, by far the highest breakdown rate was found for β‐carotene, followed by lycopene. Bleaching of carotenoid mixtures mediated by NaOCl, addition of azo‐bis‐isobutyronitril (AIBN), and the photoirradiation of carotenoid mixtures by natural sunlight lead to the following sequence of breakdown rates: lycopene > β‐carotene > zeaxanthin > lutein.The slow degradation of the xanthophylls zeaxanthin and lutein may be suggested to explain the majority of zeaxanthin and lutein in the retina of man and other species. In correspondence to that, the rapid degradation of β‐carotene and lycopene under the influence of natural sunlight and UV light is postulated to be the reason for the almost lack of those two carotenoids in the human retina. Nevertheless, a final proof of that theory is lacking.
(+)‐Catechin as antioxidant: mechanisms preventing human plasma oxidation and activity in red wines
Authors: Lotito Silvina B. , Fraga César G. 
Published: December 2008

AbstractWe evaluated the antioxidant effect of (+)‐catechin (CTCH), in the presence of physiological antioxidant levels of ascorbic acid (AA), α‐tocopherol (AT) and beta‐carotene (BC), in human plasma oxidised with AAPH. Following a five‐hour incubation, the formation of lipid oxidation products (TBARS) was almost doubled, and the concentrations of lipid soluble antioxidants were 10 to 30% from the initial levels. In these conditions, AA was consumed within the first hour of incubation. The addition of CTCH prevented AT and BC depletion and TBARS formation, but had no effect on AA consumption. When the kinetics of oxidation were analysed CTCH oxidation preceded lipid soluble antioxidant depletion, but no consumption of CTCH was associated to AA oxidation. Considering that CTCH could contribute to the antioxidant activity of red wine, we first characterised both the antioxidant capacity and CTCH content of several wines. The wines with highest content of CTCH and antioxidant activity were also the most effective in preventing AAPH‐mediated oxidation of plasma vitamin E. Results support the idea that CTCH could have a role as a physiological antioxidant in human plasma, and that CTCH of wine could contribute to the antioxidant status of human plasma.
The role of oxidative stress and NF‐κB activation in late diabetic complications
Authors: Mohamed Abdel Khalek , Bierhaus Angelika , Schiekofer Stephan , Tritschler Hans , Ziegler Reinhard , Nawroth Peter P. 
Published: December 2008

AbstractA common endpoint of hyperglycemia dependent cellular changes is the generation of reactive oxygen intermediates (ROIs) and the presence of elevated oxidative stress. Therefore, oxidative stress is supposed to play an important role in the development of late diabetic complications. Formation of advanced glycation end products (AGE's) due to elevated nonenzymatic glycation of proteins, lipids and nucleic acids is accompanied by oxidative, radical‐generating reactions and thus represents a major source for oxygen free radicals under hyperglycemic conditions. Once formed, AGE's can influence cellular function by binding to several binding sites including the receptor for AGE's, RAGE. Binding of AGE's (and other ligands) to RAGE results in generation of intracellular oxidative stress and subsequent activation of the redox‐sensitive transcription factor NF‐κB in vitro and in vivo. Consistently, activation of NF‐κB in diabetic patients correlates with the quality of glycemic control and can be reduced by treatment with the antioxidant α‐lipoic acid. The development of techiques allowing for a tissue culture independent measurement of NF‐κB activation in patients with diabetes mellitus gives insights into the molecular mechanisms linking diabetes mellitus and hyperglycemia with formation of advanced glycated endproducts and generation of oxidative stress finally resulting in oxidative stress mediated cellular activation.
Effect of a diet supplemented with thioproline on murine macrophage function in a model of premature ageing
Authors: Correa R. , Blanco B. , Del Río M. , Víctor V. , Guayerbas N. , Medina S. , De La Fuente M. 
Published: December 2008

AbstractA previous study has shown that diet supplementation with thioproline (thiazolidine‐4‐carboxylic acid, TCA), an intracellular sulfhydril antioxidant and free radical scavenger, stimulates lymphocyte functions in old mice. In the present work, the effect of thioproline ingestion on the phagocytic functions of peritoneal macrophages, namely adherence, chemotaxis, phagocytosis and superoxide anion production was studied in adult female OF1‐Swiss mice, that were fed thioproline (0.1% w/w) for five weeks, starting this ingestion at the age of 22 ± 2 weeks. Mice were divided into a fast and a slow group based on their exploratory activity, which was assessed by their performance in a T‐shaped maze. Slow mice showed a worse phagocytic activity with respect to fast animals. After thioproline treatment, a stimulation of all the functions studied as well as a neutralization of the superoxide radical were observed. The effect of this antioxidant was stronger in the slow than in the fast group. Thus, a diet supplemented with thioproline may enhance the immune functions, especially when they are depressed.
Thiols in formaldehyde dissimilation and detoxification
Authors: Duine Johannis A. 
Published: December 2008

AbstractGlutathione is not a universal coenzyme for formaldehyde oxidation. MySH (mycothiol, 1‐O‐(2′‐[N‐acetyl‐L‐cysteinyl]amido‐2′‐deoxy‐/propto‐D‐glucopyranosyl)‐D‐myo‐inositol) is GSH's counterpart as coenzyme in formaldehyde dehydrogenase from certain Gram‐positive bacteria. However, formaldehyde dissimilation and detoxification not only proceed via thiol‐dependent but also via thiol‐independent dehydrogenases. The distinct structures and enzymatic properties of MySH‐dependent and GSH‐dependent formaldehyde dehydrogenases could provide clues for development of selective drugs against pathogenic Mycobacteria. It is to be expected that other new types of thiol‐dependent formaldehyde dehydrogenases will be discovered in the future. Indications exist that the product of thiol‐dependent formaldehyde oxidation, the thiol formate ester, is not only hydrolytically converted into thiol and formate but can also be oxidatively converted in some cases by a molybdoprotein aldehyde dehydrogenase into the corresponding carbonate ester, decomposing spontaneously into CO2 and the thiol.
AhpC, oxidative stress and drug resistance in Mycobacterium tuberculosis
Authors: Sherman David R. , Mdluli Khisimuzi , Hickey Mark J. , Barry, III Clifton E. , Kendall Stover C. 
Published: December 2008

AbstractThe Mycobacterium tuberculosis AhpC is similar to a family of bacterial and eukaryotic antioxidant proteins with alkylhydroperoxidase (Ahp) and thioredoxin‐dependent peroxidase (TPx) activities. AhpC expression is associated with resistance to the front‐line antitubercular drug isoniazid in the naturally resistant organisms E. coli and M. smegmatis. We identified several isoniazid‐resistant M. tuberculosis isolates with ahpC promoter mutations resulting in AhpC overexpression. These strains were more resistant to cumene hydroperoxide than were wild‐type strains. However, these strains were unchanged in their sensitivity to isoniazid, refuting a role for AhpC in detoxification of this drug. All the isoniazid‐resistant, AhpC‐overexpressing strains were also deficient in activity of the mycobacterial catalase‐peroxidase KatG. KatG, the only known catalase in M. tuberculosis, is required for activation of isoniazid. We propose that compensatory ahpC promoter mutations are selected from KatG‐deficient, isoniazid‐resistant M. tuberculosis during infections, to mitigate the added burden imposed by organic peroxides on these strains.
Superoxide production by dinitrophenyl‐ derivatized thioredoxin reductase ‐ a model for the mechanism and correlation to immunostimulation by dinitrohalobenzenes
Authors: Arnér Elias S.J. 
Published: December 2008

AbstractMammalian thioredoxin reductase catalyzes NADPH dependent reduction of a wide variety of substrates and plays a central role in redox regulation and antioxidant defence. Recently the enzyme was discovered to be a selenoprotein with a catalytically active penultimate selenocysteine residue. Dinitrohalobenzenes irreversibly inhibit the enzyme with a concomitant induction of an NADPH oxidase activity, producing superoxide. A model explaining the reactivity of dinitrohalobenzenes with thioredoxin reductase is presented, involving dinitrophenyl‐derivatization of both the selenocysteine residue and its neighboring cysteine residue, reduction by NADPH of the enzyme‐bound flavin in dinitrophenyl‐alkylated enzyme (dnp‐TrxR), followed by two consecutive one‐electron transfers from the flavin to nitro groups of the dnp‐moieties in dnp‐TrxR, forming nitro anion radicals. The nitro radicals react with oxygen to form superoxide, again generating dnp‐TrxR with an oxidized flavin, which may then follow another cycle of NADPH‐dependent superoxide production. Dinitrohalobenzene compounds are well known for their immunostimulatory properties. Here it is proposed that the inflammatory components of this immunostimulation can be mediated by interaction with the thioredoxin system, via effects on cell function by superoxide production, oxidative stress and increased extracellular levels of thioredoxin.
Vitamin B6 enzymes participating in selenium amino acid metabolism
Authors: Soda Kenji , Oikawa Tadao , Esaki Nobuyoshi 
Published: December 2008

AbstractVarious vitamin B6 enzymes play important roles in mammalian and microbial metabolism of selenium amino acids. Selenocysteine is synthesized from selenohomocysteine by catalysis of cystathionine β‐synthase and cystathionine γ‐lyase, which both require pyridoxal phosphate. Selenocysteine β‐lyase, a new B6‐enzyme, exclusively catalyzes β‐elimination of selenocysteine, and occurs in mammalian systems and bacteria. Methionine γ‐lyase, cysteine desulfurase, cysteine sulfinate desulfinase, and D‐selenocystine α, β‐lyase, which are B6‐enzymes, act on cysteine, cysteine sulfinate, D‐cystine, and their derivatives, and their selenium counterparts indiscriminately. Their reaction mechanisms are comparatively described.
The selenoprotein thioredoxin reductase is expressed in peripheral blood monocytes and THP1 human myeloid leukemia cells ‐ regulation by 1,25‐dihydroxyvitamin D3and selenite
Authors: Schütze Norbert , Fritsche Jana , Ebert‐Dümig Regina , Schneider Doris , Köhrle Josef , Andreesen Reinhard , Kreutz Marina , Jakob Franz 
Published: December 2008

Abstract1,25(OH)2Vitamin D3(1,25(OH)2D3) and adhesion propagate monocyte differentiation. We identified the selenoprotein thioredoxin reductase (TrxR) as a new molecular target for 1,25(OH)2D3in monocytes during this process. In THP1 monocytic leukemia cells 1,25(OH)2D3stimulated TrxR mRNA levels 2—4‐fold by 4—8 h and enhanced TrxR activity (60%) (as measured by the dithionitrobenzole‐assay) after 24 h, which declined below baseline after 96 h. The addition of 100 nM selenite enhanced (approx. 50%) basal and stimulated enzyme activity in THP1 cells. The relative stimulation by 1,25(OH)2D3was very similar but peak levels were sustained in THP1 cells up to 48 h. Human peripheral blood monocytes (PBM) of different donors showed very low basal TrxR steady state mRNA levels which were markedly enhanced (as analyzed by Northern blotting) after 4 h of adherence to culture dishes. 1,25(OH)2D3(100 nM) further stimulated TrxR mRNA expression (4 h, 3‐fold). TrxR enzyme activity mirrored the mRNA changes. Basal activity was stimulated approx. 25% by adhesion in culture alone and was further stimulated (∼15%) by 1,25(OH)2D3after 4 h. By 24 h similar results were achieved but the effect of 1,25(OH)2D3could be seen in the presence of 100 nM selenium only. The expression of TrxR and its regulation by 1,25(OH)2D3and selenite in monocytes might be important for their induction of differentiation and maintenance of function.