Digitala Vetenskapliga Arkivet

Change search
Refine search result
12 51 - 65 of 65
CiteExportLink to result list
Permanent link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
Rows per page
  • 5
  • 10
  • 20
  • 50
  • 100
  • 250
Sort
  • Standard (Relevance)
  • Author A-Ö
  • Author Ö-A
  • Title A-Ö
  • Title Ö-A
  • Publication type A-Ö
  • Publication type Ö-A
  • Issued (Oldest first)
  • Issued (Newest first)
  • Created (Oldest first)
  • Created (Newest first)
  • Last updated (Oldest first)
  • Last updated (Newest first)
  • Disputation date (earliest first)
  • Disputation date (latest first)
  • Standard (Relevance)
  • Author A-Ö
  • Author Ö-A
  • Title A-Ö
  • Title Ö-A
  • Publication type A-Ö
  • Publication type Ö-A
  • Issued (Oldest first)
  • Issued (Newest first)
  • Created (Oldest first)
  • Created (Newest first)
  • Last updated (Oldest first)
  • Last updated (Newest first)
  • Disputation date (earliest first)
  • Disputation date (latest first)
Select
The maximal number of hits you can export is 250. When you want to export more records please use the Create feeds function.
  • 51.
    Sari, Gulce
    et al.
    Marmara Univ, Fac Med, Med Biochem, Istanbul, Turkey..
    Musuruni, Sravani
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Analytical Chemistry.
    Wicher, Grzegorz
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Neuro-Oncology.
    Mi, Jia
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Analytical Chemistry. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Bergquist, Jonas
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Analytical Chemistry.
    Karademir, Betul
    Marmara Univ, Fac Med, Med Biochem, Istanbul, Turkey..
    Heat shock proteins in proteasome inhibitor related neuropathy2015In: Free Radical Biology & Medicine, ISSN 0891-5849, E-ISSN 1873-4596, Vol. 86, no Suppl. 1, p. S27-S27Article in journal (Other academic)
  • 52.
    Sari-Kaplan, Gulce
    et al.
    Marmara Univ, Dept Biochem, Fac Med, Genet & Metab Dis Res & Invest Ctr, Istanbul, Turkey.;Okan Univ, Dept Genet & Bioengn, Fac Engn, Istanbul, Turkey..
    Musunuri, Sravani
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Analytical Chemistry.
    Wicher, Grzegorz
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Neuro-Oncology.
    Jung, Tobias
    German Inst Human Nutr Potsdam Rehbrucke, Dept Mol Toxicol, Potsdam, Germany..
    Mi, Jia
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Analytical Chemistry.
    Hacioglu-Bay, Husniye
    Marmara Univ, Fac Med, Dept Anat, Istanbul, Turkey..
    Bergquist, Jonas
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Analytical Chemistry.
    Grune, Tilman
    German Inst Human Nutr Potsdam Rehbrucke, Dept Mol Toxicol, Potsdam, Germany..
    Karademir, Betul
    Marmara Univ, Dept Biochem, Fac Med, Genet & Metab Dis Res & Invest Ctr, Istanbul, Turkey..
    Peripheral neuropathy as the side effect of proteasome inhibitors bortezomib and carfilzomib2016In: Free Radical Biology & Medicine, ISSN 0891-5849, E-ISSN 1873-4596, Vol. 96, p. S17-S17Article in journal (Other academic)
  • 53.
    Sasada, T.
    et al.
    Department of Biological Responses, Institute for Virus Research, Kyoto University, Kyoto, Japan.
    Nakamura, H.
    Department of Biological Responses, Institute for Virus Research, Kyoto University, Kyoto, Japan.
    Ueda, S.
    Department of Biological Responses, Institute for Virus Research, Kyoto University, Kyoto, Japan.
    Sato, N.
    Department of Biological Responses, Institute for Virus Research, Kyoto University, Kyoto, Japan.
    Kitaoka, Y.
    Department of Biological Responses, Institute for Virus Research, Kyoto University, Kyoto, Japan.
    Gon, Y.
    Department of Biological Responses, Institute for Virus Research, Kyoto University, Kyoto, Japan.
    Takabayashi, A.
    Department of Surgery, Tazuke Kofukai Kitano Hospital Medical Institute, Osaka, Japan.
    Spyrou, Giannis
    Medical Nobel Institute for Biochemistry, Department of Medical Biochemistry and Biophysics, Karolinska Institute, Stockholm, Sweden.
    Holmgren, Arne
    Medical Nobel Institute for Biochemistry, Department of Medical Biochemistry and Biophysics, Karolinska Institute, Stockholm, Sweden.
    Yodoi, J.
    Department of Biological Responses, Institute for Virus Research, Kyoto University, Kyoto, Japan.
    Possible involvement of thioredoxin reductase as well as thioredoxin in cellular sensitivity to cis-diamminedichloroplatinum (II)1999In: Free Radical Biology & Medicine, ISSN 0891-5849, E-ISSN 1873-4596, Vol. 27, no 5-6, p. 504-514Article in journal (Refereed)
    Abstract [en]

    The thioredoxin (TRX) system, composed of nicotinamide adenine dinucleotide phosphate (reduced form), TRX, and TRX reductase (TRXR), has multiple biologic functions via thiol-mediated redox control. In this study, we investigated the relationship between intracellular TRXR levels and cellular sensitivity to cis-diamminedichloroplatinum (II) (CDDP). HeLa, a human cervical carcinoma cell line, cultured with CDDP showed a time- and dose-dependent reduction of intracellular TRXR activity, which was well correlated with the decrease in cell viability after exposure to CDDP. In a cell-free system, CDDP was found to directly inactivate the reduced form of purified human TRXR. The CDDP-resistant variants of HeLa cells, established by continuous exposure to CDDP, exhibited an increased expression and activity of TRXR as well as TRX compared with the parental cells. In addition, sodium selenate, an inhibitor of TRXR, was found to increase the susceptibility to CDDP in the CDDP-resistant cells. Moreover, the HeLa cells transfected with an antisense TRXR RNA expression vector to reduce the intracellular enzyme activity displayed an enhanced sensitivity to CDDP. Taken together with previous reports on TRX, these results indicate the possible involvement of TRXR as well as TRX in the cellular sensitivity and resistance to CDDP.

  • 54.
    Sundelin, Staffan P.
    et al.
    Linköping University, Department of Neuroscience and Locomotion, Ophthalmology. Linköping University, Department of Neuroscience and Locomotion, Pathology. Linköping University, Faculty of Health Sciences.
    Nilsson, Sven Erik
    Linköping University, Department of Neuroscience and Locomotion, Ophthalmology. Linköping University, Department of Neuroscience and Locomotion, Pathology. Linköping University, Faculty of Health Sciences.
    Lipofuscin-formation in retinal pigment epithelial cells is reduced by antioxidants2001In: Free Radical Biology & Medicine, ISSN 0891-5849, E-ISSN 1873-4596, Vol. 31, no 2, p. 217-225Article in journal (Refereed)
    Abstract [en]

    The accumulation of lipofuscin by retinal pigment epithelium may be an important feature in the pathogenesis of age-related macular degeneration, suggesting the possibility that this common cause of blindness might be prevented or delayed by antioxidants. In support of this idea, we now report significantly reduced formation of lipofuscin when the antioxidant substances lutein, zeaxanthin, lycopene (carotenoids), or α-tocopherol were added to rabbit and bovine (calf) retinal pigment epithelial (RPE) cells exposed to normobaric hyperoxia (40%) and photoreceptor outer segments. Rabbit and calf RPE cells were grown for 2 weeks with addition of one of the test substances every 48 h. The cellular uptake of carotenoids and α-tocopherol was assayed by HPLC after 2 weeks. The lipofuscin-content was measured by static fluorometry (rabbit cells) or by image analysis (calf cells). Both rabbit and calf RPE showed similar results with significantly lower amounts of lipofuscin in antioxidant-treated cells. The effect of carotenoids is especially interesting, since the result is not dependent on their protective effect against photo-oxidative reactions. The chain-breaking abilities of these antioxidants in peroxidative reactions of lipid membranes and quenching of free radicals seem to be of importance for inhibition of lipofuscin formation.

  • 55.
    Sundelin, Staffan P.
    et al.
    Linköping University, Department of Neuroscience and Locomotion, Ophthalmology. Linköping University, Faculty of Health Sciences.
    Nilsson, Sven Erik G.
    Linköping University, Department of Neuroscience and Locomotion, Ophthalmology. Linköping University, Faculty of Health Sciences.
    Brunk, Ulf
    Linköping University, Department of Neuroscience and Locomotion, Pathology. Linköping University, Faculty of Health Sciences.
    Lipofuscin-formation in cultured retinal pigment epithelial cells is related to their melanin content2001In: Free Radical Biology & Medicine, ISSN 0891-5849, E-ISSN 1873-4596, Vol. 30, no 1, p. 74-81Article in journal (Refereed)
    Abstract [en]

    Age-related macular degeneration (AMD), the leading cause of blindness in the developed world, is accompanied by degeneration of the retinal pigment epithelial (RPE) cells. There is an inverse correlation between the melanin content of the eye and the incidence of AMD. Lipofuscin (LF)-accumulation in RPE cells accompanies the process of aging, and may also be related to AMD. This study was designed to evaluate the effect of melanin/melanosomes on the rate of LF formation in cultured rabbit and bovine RPE cells subjected to oxidative stress (40% normobaric O2) and daily supplementation with photoreceptor outer segments for 4 weeks. The LF content was measured at 0, 2, and 4 weeks in RPE cells from pigmented and albino rabbits, as well as in pigment-rich and pigment-poor bovine cells. Albino rabbit and pigment-poor bovine cells accumulated significantly higher amounts of LF than pigmented rabbit cells and pigment-rich bovine RPE cells after both 2 and 4 weeks of exposure. Autometallography of melanin-containing cells, without previous exposure to ammonium sulfide, showed a positive outcome, indicating either the occurrence of pre-existing iron-sulphur clusters or an extremely high intrinsic reducing capacity. These results suggest that melanin acts as an efficient antioxidant, perhaps by interacting with transition metals.

  • 56.
    Teixeira, Pedro Filipe
    et al.
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics.
    Pinho, Catarina Moreira
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics.
    Branca, Rui M.
    Lehtio, Janne
    Levine, Rodney L.
    Glaser, Elzbieta
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics.
    In vitro oxidative inactivation of human presequence protease (hPreP)2012In: Free Radical Biology & Medicine, ISSN 0891-5849, E-ISSN 1873-4596, Vol. 53, no 11, p. 2188-2195Article in journal (Refereed)
    Abstract [en]

    The mitochondrial peptidasome called presequence protease (Prep) is responsible for the degradation of presequences and other unstructured peptides including the amyloid-beta, peptide, whose accumulation may have deleterious effects on mitochondrial function. Recent studies showed that PreP activity is reduced in Alzheimer disease (AD) patients and AD mouse models compared to controls, which correlated with an enhanced reactive oxygen species production in mitochondria. In this study, we have investigated the effects of a biologically relevant oxidant, hydrogen peroxide (H2O2), on the activity of recombinant human PreP (hPreP). H2O2 inhibited hPreP activity in a concentration-dependent manner, resulting in oxidation of amino acid residues (detected by carbonylation) and lowered protein stability. Substitution of the evolutionarily conserved methionine 206 for leucine resulted in increased sensitivity of hPreP to oxidation, indicating a possible protective role of M2O6 as internal antioxidant. The activity of hPreP oxidized at low concentrations of H2O2 could be restored by methionine sulfoxide reductase A (MsrA), an enzyme that localizes to the mitochondrial matrix, suggesting that hPreP constitutes a substrate for MsrA. In summary, our in vitro results suggest a possible redox control of hPreP in the mitochondrial matrix and support the protective role of the conserved methionine 206 residue as an internal antioxidant.

  • 57. Veneskoski, Marja
    et al.
    Turunen, S. Pauliina
    University of Oulu, 90014 Oulu, Finland.
    Kummu, Outi
    Nissinen, Antti
    Rannikko, Sirpa
    Levonen, Anna-Liisa
    Hörkkö, Sohvi
    Specific recognition of malondialdehyde and malondialdehyde acetaldehyde adducts on oxidized LDL and apoptotic cells by complement anaphylatoxin C3a.2011In: Free Radical Biology & Medicine, ISSN 0891-5849, E-ISSN 1873-4596, Vol. 51, no 4, p. 834-43Article in journal (Refereed)
    Abstract [en]

    Oxidatively modified low-density lipoproteins (Ox-LDL) and complement anaphylatoxins C3a and C5a are colocalized in atherosclerotic lesions. Anaphylatoxin C3a also binds and breaks bacterial lipid membranes and phosphatidylcholine liposomes. The role of oxidized lipid adducts in C3a binding to Ox-LDL and apoptotic cells was investigated. Recombinant human C3a bound specifically to low-density lipoprotein and bovine serum albumin modified with malondialdehyde (MDA) and malondialdehyde acetaldehyde (MAA) in chemiluminescence immunoassays. No binding was observed to native proteins, LDL oxidized with copper ions (CuOx-LDL), or phosphocholine. C3a binding to MAA-LDL was inhibited by two monoclonal antibodies specific for MAA-LDL. On agarose gel electrophoresis, C3a comigrated with MDA-LDL and MAA-LDL, but not with native LDL or CuOx-LDL. C3a bound to apoptotic cells in flow cytometry. C3a opsonized MAA-LDL and was taken up by J774A.1 macrophages in immunofluorescence analysis. Complement-activated human serum samples (n=30) showed increased C3a binding to MAA-LDL (P<0.001) and MDA-LDL (P<0.001) compared to nonactivated samples. The amount of C3a bound to MAA-LDL was associated with total complement activity, C3a desArg concentration, and IgG antibody levels to MAA-LDL. Proteins containing MDA adducts or MAA adducts may bind C3a in vivo and contribute to inflammatory processes involving activation of the complement system in atherosclerosis.

  • 58.
    Weibrecht, Irene
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
    Böhmer, Sylvia-Annette
    Dagnell, Markus
    Kappert, Kai
    Östman, Arne
    Böhmer, Frank-D.
    Oxidation sensitivity of the catalytic cysteine of the protein-tyrosine phosphatases SHP-1 and SHP-22007In: Free Radical Biology & Medicine, ISSN 0891-5849, E-ISSN 1873-4596, Vol. 43, no 1, p. 100-110Article in journal (Refereed)
    Abstract [en]

    Reversible oxidation of the catalytic cysteine of protein-tyrosine phosphatases (PTPs) has emerged as a putative mechanism of activity regulation by physiological cell stimulation with growth factors, and by cell treatments with adverse agents such as UV irradiation. We compared SHP-1 and SHP-2, two structurally related cytoplasmic protein-tyrosine phosphatases with different cellular functions and cell-specific expression patterns, for their intrinsic susceptibility to oxidation by H(2)O(2). The extent of oxidation was monitored by detecting the modification of the PTP catalytic cysteine by three different methods, including a modified in-gel PTP assay, alkylation with a biotinylated iodoacetic acid derivative, and an antibody against oxidized PTPs. Dose-response curves for oxidation of the catalytic domains of SHP-1 and SHP-2 were similar. SHP-1 and -2 require relatively high H(2)O(2) concentrations for oxidation (half-maximal oxidation at 0.1-0.5 mM). For SHP-1, the SH2 domains had a significant protective function with respect to oxidation. In EOL-1 cells, SHP oxidation by exogenous H(2)O(2) in general and SHP-2 oxidation in particular was strongly diminished compared to HEK293 cells, at least partially related to a generally lower oxidant sensitivity of the EOL-1 cells. The data suggest that the differential cell functions of SHP-1 and SHP-2 are not related to differences in oxidation sensitivity. The modulating effects of SH2 domains for oxidation of these PTPs are in support of an enhanced oxidation susceptibility of activated SHPs.

  • 59.
    Welander, Hedvig
    et al.
    Uppsala Universitet.
    Wiberg, Henning
    KTH, School of Chemical Science and Engineering (CHE), Chemistry, Applied Physical Chemistry.
    Emmer, Åsa
    KTH, School of Chemical Science and Engineering (CHE), Chemistry, Applied Physical Chemistry.
    Lannfelt, Lars
    Uppsala Universitet.
    Ingelsson, Martin
    Uppsala Universitet.
    Bergström, Joakim
    Uppsala Universitet.
    Histidine 50 is a crucial residue for alpha-synuclein aggregation induced by lipid peroxidation-derived aldehydes2012In: Free Radical Biology & Medicine, ISSN 0891-5849, E-ISSN 1873-4596, Vol. 53, no Suppl 1, p. S248-S249Article in journal (Refereed)
  • 60. Yin, D.
    et al.
    Lingnert, Hans
    Ekstrand, Bo
    SIK – Institutet för livsmedelsforskning.
    Brunk, U.T.
    Fenton reagents may not initiate lipid peroxidation in an emulsified linoleic acid model system1992In: Free Radical Biology & Medicine, ISSN 0891-5849, E-ISSN 1873-4596, Vol. 13, no 5, p. 543-556Article in journal (Refereed)
    Abstract [en]

    This study includes two parts. First, the Fe2+ autooxidation and chelation processes in the presence of the chelators ethylenediaminetetraacetic acid (EDTA) and diethylenetriamine pentaacetic acid (DTPA) were studied by measuring UV light absorbance alterations. Competition for Fe3+ between chelators and water or phosphate buffer (PB) ions was confirmed. The addition of EDTA or DTPA to Fe3+ in water or PB only slowly turned the water/PB-Fe3+ complexes to EDTA-Fe3+ or DTPA-Fe3+ complexes. In the second part of this study, the initiation mechanisms of Tween 20 emulsified linoleic acid peroxidation under stimulation by chelator-Fe-O2 complexes were studied by measuring changes in UV light absorbance following diene conjugation. Fe3+ in the presence of EDTA or DTPA did not stimulate diene conjugation. Fe2+ (0.10 mM) and EDTA (0.11 mM) stimulated diene conjugation of the linoleic acid emulsion, but only after apparent Fe2+ autooxidation. Fe2+ and DTPA, as well as premixed DTPA-Fe2+ complex, resulted in very fast diene conjugation in a wide range of concentrations. A nonlinear, mainly square root relation between Fe2+ concentration and peroxidation rate was noted. Superoxide dismutase (SOD), catalase, and mannitol did not prevent the lipid peroxidation. H2O2 substantially decreased the DTPA-Fe2+ stimulated, otherwise rapid, diene conjugation but slightly enhanced the slower one stimulated by EDTA-Fe2+. Without ambient oxygen, Fenton reagents did not result in 'H abstraction-related diene conjugation. The findings suggest that 'OH resulting from Fenton reagents may not be the main cause for the initiation of peroxidation in this model system. Furthermore, a study with different combinations of Fe2+ and Fe3+ did not support the Fe2+/Fe3+ (1:1) optimum ratio hypothesis. We therefore conclude that perferryl ions or chelator-Fe-O2 complexes may be responsible for the first-chain initiation 2 of lipid peroxidation, at least in this model system.

  • 61.
    Yu, Zhengquan
    et al.
    Linköping University, Department of Neuroscience and Locomotion, Pathology. Linköping University, Department of Neuroscience and Locomotion, Neurosurgery. Linköping University, Faculty of Health Sciences.
    Persson, Lennart
    Linköping University, Department of Neuroscience and Locomotion, Pathology. Linköping University, Department of Medicine and Care, Pulmonary Medicine. Linköping University, Faculty of Health Sciences.
    Eaton, John Wallace
    Linköping University, Department of Neuroscience and Locomotion, Pathology. Linköping University, Faculty of Health Sciences.
    Brunk, Ulf
    Linköping University, Department of Neuroscience and Locomotion, Pathology. Linköping University, Faculty of Health Sciences.
    Intralysosomal iron: a major determinant of oxidant-induced cell death2003In: Free Radical Biology & Medicine, ISSN 0891-5849, E-ISSN 1873-4596, Vol. 34, no 10, p. 1243-1252Article in journal (Refereed)
    Abstract [en]

    As a result of continuous digestion of iron-containing metalloproteins, the lysosomes within normal cells contain a pool of labile, redox-active, low-molecular-weight iron, which may make these organelles particularly susceptible to oxidative damage. Oxidant-mediated destabilization of lysosomal membranes with release of hydrolytic enzymes into the cell cytoplasm can lead to a cascade of events eventuating in cell death (either apoptotic or necrotic depending on the magnitude of the insult). To assess the importance of the intralysosomal pool of redox-active iron, we have temporarily blocked lysosomal digestion by exposing cells to the lysosomotropic alkalinizing agent, ammonium chloride (NH4Cl). The consequent increase in lysosomal pH (from ca. 4.5 to > 6) inhibits intralysosomal proteolysis and, hence, the continuous flow of reactive iron into this pool. Preincubation of J774 cells with 10 mM NH4Cl for 4 h dramatically decreased apoptotic death caused by subsequent exposure to H2O2, and the protection was as great as that afforded by the powerful iron chelator, desferrioxamine (which probably localizes predominantly in the lysosomal compartment). Sulfide-silver cytochemical detection of iron revealed a pronounced decrease in lysosomal content of redox-active iron after NH4Cl exposure, probably due to diminished intralysosomal digestion of iron-containing material coupled with continuing iron export from this organelle. Electron paramagnetic resonance experiments revealed that hydroxyl radical formation, readily detectable in control cells following H2O2 addition, was absent in cells preexposed to 10 mM NH4Cl. Thus, the major pool of redox-active, low-molecular-weight iron may be located within the lysosomes. In a number of clinical situations, pharmacologic strategies that minimize the amount or reactivity of intralysosomal iron should be effective in preventing oxidant-induced cell death.

  • 62.
    Yuan, Xi Ming
    et al.
    Linköping University, Department of Neuroscience and Locomotion, Pathology. Linköping University, Faculty of Health Sciences.
    Li, Wei
    Linköping University, Department of Neuroscience and Locomotion, Pathology. Linköping University, Faculty of Health Sciences.
    Brunk, Ulf
    Linköping University, Department of Neuroscience and Locomotion, Pathology. Linköping University, Faculty of Health Sciences.
    Dalen, Helge
    Department of Pathology, The Gade Institute, University of Bergen, Bergen, Norway.
    Chang, Yi Hsin
    Department of Molecular Pharmacology and Toxicology, School of Pharmacy, University of Southern California, Los Angeles, CA, USA.
    Sevanian, Alex
    Department of Molecular Pharmacology and Toxicology, School of Pharmacy, University of Southern California, Los Angeles, CA, USA.
    Lysosomal destabilization during macrophage damage induced by cholesterol oxidation products2000In: Free Radical Biology & Medicine, ISSN 0891-5849, E-ISSN 1873-4596, Vol. 28, no 2, p. 208-218Article in journal (Refereed)
    Abstract [en]

    We have previously shown that oxidized low-density lipoprotein (LDL) induces damage to the macrophage lysosomal membranes, with ensuing leakage of lysosomal contents and macrophage cell death. Cholesterol oxidation products (ChOx) have been reported to be the major cytotoxic components of oxidized LDL/LDL and also to stimulate cholesterol accumulation in vascular cells. In the present study, we characterized the initial events during macrophage damage induced by cholesterol oxidation products (ChOx). Within 24 h of exposure, ChOx caused lysosomal destabilization, release to the cytosol of the lysosomal marker-enzyme cathepsin D, apoptosis, and postapoptotic necrosis. Enhanced autophagocytosis and chromatin margination was found 12 h after the exposure to ChOx, whereas apoptosis and postapoptotic necrosis was pronounced 24 and 48 h after the exposure. Some lysosomal vacuoles were then filled with degraded cellular organelles, indicating phagocytosis of apoptotic bodies by surviving cells. Because caspase-3 activation was detected in the ChOx-exposed cells, lysosomal destabilization may associate with the leakage of lysosomal enzymes, and activation of the caspase cascade. MnSOD mRNA levels were markedly increased after 24 h of exposure to ChOx, suggesting associated induction of mitochondrial protection repair or turnover. We conclude that ChOx-induced damage to lysosomes and mitochondria are sequelae to the cascade of oxysterol cytotoxic events. The early disruption of lysosomes induced by ChOx, with resultant autophagocytosis may be a critical event in apoptosis and/or necrosis of macrophages/foam cells during the development of atherosclerotic lesions.

  • 63.
    Zheng, Lin
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Geriatric. Linköping University, Faculty of Health Sciences.
    Kågedal, Katarina
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
    Dehvari, Nodi
    Karolinska Institutet, Stockholm.
    Benedikz, Eirikur
    Karolinska Institutet, Stockholm.
    Cowburn, Richard
    AstraZeneca R&D.
    Marcusson, Jan
    Linköping University, Department of Clinical and Experimental Medicine, Geriatric. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Geriatric Medicine.
    Terman, Alexei
    Linköping University, Department of Clinical and Experimental Medicine, Geriatric. Linköping University, Faculty of Health Sciences.
    Oxidative stress induces macroautophagy of amyloid beta-protein and ensuing apoptosis2009In: Free Radical Biology & Medicine, ISSN 0891-5849, E-ISSN 1873-4596, Vol. 46, no 3, p. 422-429Article in journal (Refereed)
    Abstract [en]

    There is increasing evidence for the toxicity of intracellular amyloid beta-protein (A beta) to neurons and the involvement of lysosomes in this process in Alzheimer disease (AD). We have recently shown that oxidative stress, a recognized determinant of AD. enhances macroautophagy and leads to intralysosomal accumulation of A beta in Cultured neuroblastoma cells. We hypothesized that oxidative stress promotes AD by stimulating macroautophagy of A that further may induce cell death by destabilizing lysosomal membranes. To investigate such possibility, we compared the effects of hyperoxia (40% ambient oxygen) in cultured HEK293 cells that were transfected with an empty vector (Vector), wild-type APP (APPwt), or Swedish mutant APP (APPswe). Exposure to hyperoxia for 5 days increased the number of cells with A beta-containing lysosomes, as well as the number of apoptotic cells, compared to normoxic conditions. The rate of apoptosis in all three cell lines demonstrated dependence on intralysosomal A beta content (Vector<APPwt<APPswe). Furthermore, the degree of apoptosis was positively correlated with lysosomal membrane permeabilization, whereas inhibitors Of macroautophagy and lysosomal function decreased oxidant-induced apoptosis and diminished the differences in apoptotic response between different cell lines. These results suggest that oxidative stress can induce neuronal death through macroautophagy of A beta and consequent lysosomal membrane permeabilization, which may help explain the mechanisms behind neuronal loss in AD.

  • 64.
    Zhou, Jie
    et al.
    Institute of Biochemistry I, Faculty of Medicine, Johann Wolfgang Goethe-University Frankfurt, Germany.
    Eleni, Chantzoura
    Biochemical Research Foundation, Academy of Athens, Greece.
    Spyrou, Giannis
    Biochemical Research Foundation, Academy of Athens, Greece.
    Brüne, Bernhard
    Institute of Biochemistry I, Faculty of Medicine, Johann Wolfgang Goethe-University Frankfurt, Germany.
    The mitochondrial thioredoxin system regulates nitric oxide-induced HIF-1a protein2008In: Free Radical Biology & Medicine, ISSN 0891-5849, E-ISSN 1873-4596, Vol. 44, no 1, p. 91-98Article in journal (Refereed)
    Abstract [en]

    Hypoxia-inducible factor-1 (HIF-1), consisting of two subunits, HIF-1alpha and HIF-1beta, is a key regulator for adaptation to low oxygen availability, i.e., hypoxia. Compared to the constitutively expressed HIF-1beta, HIF-1alpha is regulated by hypoxia but also under normoxia (21% O(2)) by several stimuli, including nitric oxide (NO). In this study, we present evidence that overexpression of mitochondrial-located thioredoxin 2 (Trx2) or thioredoxin reductase 2 (TrxR2) attenuated NO-evoked HIF-1alpha accumulation and transactivation of HIF-1 in HEK293 cells. In contrast, cytosolic-located thioredoxin 1 (Trx1) enhanced HIF-1alpha protein amount and activity under NO treatments. Taking into consideration that thioredoxins affect the synthesis of HIF-1alpha by altering Akt/mTOR signaling, we herein show that p42/44 mitogen-activated protein kinase and p70S6 kinase are involved. Moreover, intracellular ATP was increased in Trx1-overexpressing cells but reduced in cells overexpressing Trx2 or TrxR2, providing thus an understanding of how protein synthesis is regulated by thioredoxins.

  • 65.
    Östman, Bengt
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Michaëlsson, Karl
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm , UCR-Uppsala Clinical Research center.
    Byberg, Liisa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm , UCR-Uppsala Clinical Research center.
    Helmersson, Johanna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Oxidative Stress and Inflammation.
    Basu, Samar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Oxidative Stress and Inflammation.
    Gedeborg, Rolf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm , UCR-Uppsala Clinical Research center.
    Melhus, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm , UCR-Uppsala Clinical Research center.
    Oxidative stress and bone mineral density in elderly men: antioxidant activity of alpha-tocopherol2009In: Free Radical Biology & Medicine, ISSN 0891-5849, E-ISSN 1873-4596, Vol. 47, no 5, p. 668-673Article in journal (Refereed)
    Abstract [en]

    Oxidative stress has recently been identified as a pivotal pathogenetic factor of bone loss in mice, but its importance in humans is not clear. We aimed to investigate the association between urinary 8-iso-PGF(2 alpha) levels, a major F(2)-isoprostane and a reliable in vivo biomarker of oxidative stress, and bone mineral density (BMD), and to study whether vitamin E in the form of serum alpha-tocopherol, a scavenger of peroxyl radicals, modifies the association. In 405 men, urinary 8-iso-PGF(2 alpha) and serum alpha-tocopherol were measured at age 77 years and BMD at age 82 years. One SD increase in 8-iso-PGF(2 alpha) corresponded to an approximately 2-4% decrease in average adjusted BMD values of total body, lumbar spine, and proximal femur (all P<0.001). Serum alpha-tocopherol levels seemed to modify the association between urinary 8-iso-PGF(2 alpha) and BMD. Men with alpha-tocopherol levels below the median combined with high oxidative stress, i.e., 8-iso-PGF(2 alpha) above the median, had 7% (95% CI 3-11%) lower BMD at the lumbar spine and 5% (95% CI 2-9%) lower BMD at the proximal femur. In elderly men high oxidative stress is associated with reduced BMD, which is more pronounced in individuals with low serum levels of the antioxidant vitamin E.

    Download full text (pdf)
    FULLTEXT01
12 51 - 65 of 65
CiteExportLink to result list
Permanent link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf