bluuebunny/crossref_metadata_2025_split huggingface dataset:
Myeloperoxidase‐induced lipid peroxidation of LDL in the presence of nitrite. Protection by cocoa flavanols
Authors: Schewe Tankred , Sies Helmut 
Published: December 2008

AbstractLipid peroxidation (LPO) of low‐density lipoprotein (LDL) is believed to be a pivotal process rendering this plasma lipoprotein atherogenic. Several endogenous factors have been proposed to mediate LPO of LDL, among them myeloperoxidase (MPO), which is active in atherosclerotic lesions, and the plasma level of which has been proposed to be a prognostic parameter for cardiac events. Nitrite, a major oxidation product of nitric oxide, is substrate of MPO and a cofactor of MPO‐mediated LPO under physiological conditions. Dietary flavonoids including (‐)‐epicatechin, a major flavan‐3‐ol in cocoa products, grapes and wine, are substrates of MPO as well as potent inhibitors of LPO in LDL at micromolar concentrations. Moreover, they strongly suppress protein tyrosine nitration of LDL by MPO/nitrite or peroxynitrite. By blunting undesirable MPO‐mediated actions of nitrite, presumably via scavenging of the strong prooxidant and nitrating ˙NO2 radical, dietary flavonoids modulate NO metabolism in a favorable direction and thus counteract endothelial dysfunction. This article gives a survey on recent progress in this field with special reference to own recently published work.
A novel test for identifying genes involved in aldehyde detoxification in the yeast. Increased sensitivity of superoxide‐deficient yeast to aldehydes and their metabolic precursors
Authors: Biliński Tomasz , Kwolek Magdalena , Sas Ewelina , Krynicka Marta , Koziol Sabina , Owsiak‐Teleon Alina , Krzepilko Anna , Bartosz Grzegorz 
Published: December 2008

AbstractA novel test for the identification of genes involved in aldehyde metabolism is proposed, based on detection of altered sensitivity of the yeast to corresponding alcohols, metabolic precursors of the aldehydes. This attitude enabled to an unexpected detection increased sensitivity of mutants devoid of CuZn‐superoxide dismutase (CuZnSOD) to allyl alcohol (precursor of acrolein) and nonenol. We interpret this finding as due to inactivation of some important element of aldehyde detoxification by increased flux of superoxide in ΔCuZnSOD mutants.
Interaction of hypohalous acids and heme peroxidases with unsaturated phosphatidylcholines
Authors: Spalteholz Holger , Wenske Kathrin , Arnhold JÜRgen 
Published: December 2008

AbstractThe formation of chlorohydrins, bromohydrins, and iodohydrins from 1‐palmitoyl‐2‐oleoyl‐sn‐glycero‐3‐phosphocholine (POPC) by the myeloperoxidase‐hydrogen peroxide‐halide system was evaluated by means of matrix‐assisted laser desorption/ionisation time‐of‐flight (MALDI‐TOF) mass spectrometry. This approach allows to detect different kinds of the halogenation reaction even in one mass spectrum. Using a mixture of Cl−, Br−, I−, and SCN− at physiological concentrations, a bromination of POPC dominates by the MPO‐hydrogen peroxide‐halide system. Hypothiocyanite does apparently not react with the double bond of POPC, but increasing amounts of SCN− cause a decrease of the bromohydrin peaks. An interconversion between different hypohalous acids produced by the myeloperoxidase‐hydrogen peroxide‐halide system determines the pattern of halogenohydrins in POPC. Especially, hypochlorous acid is able to oxidise Br‐ to hypobromous acid.
Carnosine and related dipeptides as quenchers of reactive carbonyl species: From structural studies to therapeutic perspectives
Authors: Aldini Giancarlo , Facino Roberto Maffei , Beretta Giangiacomo , Carini Marina 
Published: December 2008

AbstractCarnosine (β‐alanyl‐L‐histidine) and related peptides such as homocarnosine (γ‐amino‐butyryl‐histidine), balenine β‐alanyl‐L‐3‐methylhistidine) and anserine β‐alanyl‐L‐1‐methylhistidine) are histidine‐containing dipeptides (HD) particularly abundant in excitable tissues such as nervous system and skeletal muscle. Although their biochemical role is still unknown, several evidences indicate that these endogenous compounds act as quenchers of reactive and cytotoxic carbonyl species. In this presentation we will review the structural evidences and ex vivo data supporting this hypothesis. We first elucidated the reaction mechanism of carnosine as quencher of α, β‐unsaturated aldehydes such as 4‐hydroxy‐trans‐2,3‐nonenal (HNE) and acrolein (ACR) and then demonstrated the efficacy of carnosine and related peptides as detoxifying agents of HNE in spontaneously oxidized rat skeletal muscle, by detecting the corresponding HNE‐Michael adducts in the crude biological matrix by liquid chromatography/electrospray ionization tandem mass spectrometry (LC‐ESI‐MS/MS). Finally, we set‐up and validated a sensitive, selective and specific LC‐ESI‐MS/MS method for the determination of HD and of the corresponding HNE‐Michael adducts to monitor their profile in physiological (aging) and pathological conditions (diabetes, atherosclerosis) characterized by a carbonyl‐mediated degenerative overload. The results obtained, beside to give a contribution to the understanding of the biochemical role of histidine‐dipeptides, provide a strong rational to the design of novel derivatives, active as exogenous agents able to detoxify carbonyl compounds.
Dihydroxynonene mercapturic acid, a urinary metabolite of 4‐hydroxynonenal, as a biomarker of lipid peroxidation
Authors: Peiro GÉRaldine , Alary Jacques , Cravedi Jean‐Pierre , Rathahao Estelle , Steghens Jean‐Paul , Guéraud FranÇOise 
Published: December 2008

AbstractThe objective of our study was to compare the information obtained through the use of three different urinary biomarkers of lipoperoxidation during the time course of a bromotrichloromethane (BrCCl3) induced oxidative stress in rats. These biomarkers were malondialdehyde (MDA) measured by LC/MS after derivatization, the isoprostane 8‐iso‐PGF2αmeasured by enzyme immunoassay and 1,4‐dihydroxynonene mercapturic acid (DHN‐MA), the major 4‐hydroxynonenal urinary metabolite [1], measured by LC‐MS. Male Wistar rats received a single dose of 100 μL/kg BrCCl3per osand lipid peroxidation was estimated every day for a 4‐day‐period after treatment. MDA, 8‐iso‐PGF2αand DHN‐MA significantly increased in response to BrCCl3treatment for this period of time, and DHN‐MA showed the main increase during the 24–48 h period after treatment.
Enantioselective metabolism of (R)‐ and (S)‐4‐hydroxy‐2‐nonenal in rat
Authors: Guéraud FranÇOise , Crouzet Fabienne , Alary Jacques , Rao Dinesh , Debrauwer Laurent , Laurent FranÇOis , Cravedi Jean‐Pierre 
Published: December 2008

Abstract4‐Hydroxy‐2‐nonenal (HNE) is an endogenous product of lipid peroxidation, which is believed to play a biological role in the pathogenesis of various diseases. HNE is formed as a racemic mixture of (R)‐ and (S)‐ enantiomers. These enantiomers differ in their biological properties. The aim of this study was to investigate separately the in vivo metabolism of the two HNE enantiomers in male rats after intravenous administration of the corresponding radiolabeled compounds and to compare the results with those obtained with the racemic mixture. Although the difference in the excretion rates was not statistically significant, the HPLC profiles of urinary metabolites showed qualitative and quantitative differences between the two enantiomers. The level of 3‐mercapturic acid‐1,4‐dihydroxynonane, which is considered as the major urinary metabolite of HNE, was significantly lower in the case of (S)‐HNE injected rats. In vitro studies using rat liver cytosolic incubations and HNE‐glutathione conjugate as substrate were performed to clarify the intermediate pathways involved in their metabolism. Large differences were obtained in the reduction and retro‐Michael conversion steps of the metabolism between the conjugates originating from the two enantiomers.
Antioxidants prevented oxidative injury of SR induced by Fe2+/H2O2/ascorbate system but failed to prevent Ca2+‐ATPase activity decrease
Authors: Horáková Lubica , Štrosová Miriam , Škuciová Mária 
Published: December 2008

AbstractDysfunction of sarcoplasmic reticulum (SR) Ca2+‐ATPase induced by oxidative stress may be a contributing factor to the development of serious age related diseases. Incubation of sarcoplasmic reticulum (SR) vesicles of rabbit skeletal muscles with Fe2+/H2O2/ascorbate decreased the SH group content of SR approximately to 35% and Ca2+‐ATPase activity to 50% of control not oxidized sample. Protein carbonyls increased twofold, lipid peroxidation was also significantly elevated.The antioxidant effects of trolox, the pyridoindole derivative stobadine and of the standardized extracts from bark of Pinus Pinaster Pycnogenol® (Pyc) and from leaves of Ginkgo biloba (EGb 761) were studied on oxidatively injured SR. All antioxidants exerted preventive effects against the oxidized lipids and protein SH groups of SR vesicles. Trolox and stobadine did not influence protein carbonyl formation, while flavonoid extracts prevented carbonyl generation, probably by binding to protein. The preventive effects of the antioxidants studied on lipids and protein SH groups were however not associated with protection of Ca2+‐ATPase activity. Stobadine and trolox exerted no effect on enzyme activity, Pyc and EGb 761 enhanced the inhibitory effect of Ca2+‐ATPase activity in oxidatively injured SR. Concluding, under the conditions of oxidative stress induced by Fe2+/H2O2/ascorbate against SR of rabbit skeletal muscle, the agents studied demonstrated antioxidant effects yet failed to protect Ca2+‐ATPase activity.
Oxidative damage to Ca2+‐ATPase sarcoplasmic reticulum by HOCl and protective effect of some antioxidants
Authors: Štrosová Miriam , Škuciová Mária , Horáková L'Ubica 
Published: December 2008

AbstractInjury of rabbit skeletal sarcoplasmic reticulum (SR) induced by hypochlorous acid (HOCl) was studied. HOCl inhibited Ca2+‐ATPase activity in a concentration‐dependent manner (IC50=100 μmol/l). The concentration of 13.5 μmol/l HOCl reduced the level of sulfhydryl (SH) groups by 50%, yet it did not influence the enzyme activity. In comparison with SH group oxidation and enzyme activity inhibition, a significantly longer time was necessary for the generation of protein carbonyls in SR injured by HOCl.Protective effects of some antioxidants (stobadine, trolox, EGb 761, Pycnogenol®) were studied in SR oxidatively injured by HOCl. Trolox and EGb 761 exerted a protective effect on ATPase activity and on SH groups of SR oxidatively modified by HOCl. Stobadine and Pycnogenol® inhibited markedly protein carbonyl formation. Stobadine was the only antioxidant able to scavenge HOCl. In conclusion, the protective effects of antioxidants against decrease of Ca2+‐ATPase activity induced by HOCl might be caused by protection of SH groups. The compounds with both antioxidant and Ca2+‐ATPase protecting effect offer dual defense against tissue damage occurring, e.g. in aging process.
Hydroxynonenal and uncoupling proteins: A model for protection against oxidative damage
Authors: Echtay Karim S. , Pakay Julian L. , Esteves Telma C. , Brand Martin D. 
Published: December 2008

AbstractIn this mini review we summarize recent studies from our laboratory that show the involvement of superoxide and the lipid peroxidation product 4‐hydroxynonenal in the regulation of mitochondrial uncoupling. Superoxide produced during mitochondrial respiration is a major cause of the cellular oxidative damage that may underlie degenerative diseases and ageing. Superoxide production is very sensitive to the magnitude of the mitochondrial protonmotive force, so can be strongly decreased by mild uncoupling. Superoxide is able to give rise to other reactive oxygen species, which elicit deleterious effects primarily by oxidizing intracellular components, including lipids, DNA and proteins. Superoxide‐induced lipid peroxidation leads to the production of reactive aldehydes, including 4‐hydroxynonenal. These aldehydic lipid peroxidation products are in turn able to modify proteins such as mitochondrial uncoupling proteins and the adenine nucleotide translocase, converting them into active proton transporters. This activation induces mild uncoupling and so diminishes mitochondrial superoxide production, hence protecting against disease and oxidative damage at the expense of energy production.
Inhibition of defective adenylosuccinate lyase by HNE: A neurological disease that may be affected by oxidative stress
Authors: Crifò C. , Siems W. , Soro S. , Salerno C. 
Published: December 2008

AbstractAdenylosuccinate lyase is an enzyme of fumarase superfamily that participates in the purine biosynthetic pathway, catalysing the nonhydrolytic cleavage of succinyl groups from SAICA ribotide and adenylosuccinate. Enzyme defects are associated with a human inherited disease, which arises from single point mutations to the gene and results in mild to severe psychomotor retardation, epilepsy, muscle wasting, and autistic features. Adenylosuccinate lyase activity is lost to a different extent in the patients. Diminished levels of enzyme have been attributed to loss of catalytic activity, protein instability, or environmental factors. P100A/D422Y mutation represents a feasible model for studying the effect of cell milieu on the activity of the impaired enzyme. The defective enzyme is inhibited by micromolar concentrations of trans‐4‐hydroxy‐2‐nonenal (HNE), a major product of membrane peroxidation that has been found to accumulate in brain tissues of patients with neurodegenerative disorders. It is suggested that inactivation of defective adenylosuccinate lyase by HNE and other membrane peroxidation products may account, at least in part, for the impairment of neurological functions and recurrent worsening of the symptoms.
Inhibition of ion transport ATPases by HNE
Authors: Crifò C. , Capuozzo E. , Siems W. , Salerno C. 
Published: December 2008

Abstract4‐Hydroxy‐2,3‐trans‐nonenal (HNE), a major lipid peroxidation product, has been shown to react with specific amino acid residues of proteins and alter their function. In vitro exposure of erythrocyte ghosts and neutrophil membranes to HNE results in the inhibition of ion transport ATPases. Neutrophil membrane Ca2+‐ATPase is strongly inhibited by micromolar concentrations of HNE, while HNE is considerably less effective against neutrophil Mg2+‐ATPase and the erythrocyte ghost enzymes.
Cyto‐ and genotoxic potential of β‐carotene and cleavage products under oxidative stress
Authors: Alija A.J. , Bresgen N. , Sommerburg O. , Langhans C.D. , Siems W. , Eckl P.M. 
Published: December 2008

AbstractFree radical attack on β‐carotene results in the formation of high amounts of cleavage products with prooxidant activities towards subcellular organelles such as mitochondria, a finding which could provide an explanation for the contradictory results obtained with β‐carotene in clinical efficacy and cancer prevention trials. Since primary hepatocytes proved to be very sensitive indicators for the genotoxic action of suspect mutagens/carcinogens we therefore investigated a β‐carotene cleavage products mixture (CP), apo‐8′‐β‐carotenal (apo‐8′) and β‐carotene in the primary rat hepatocyte assay in the presence and absence of oxidative stress provided by hypoxia/reoxygenation (Hy/re). The endpoints tested were: the mitotic indices, the percentages of necrotic and apoptotic cells, micronucleated cells (MN), chromosomal aberrations (CA) and sister chromatid exchanges (SCE). The results obtained indicate a genotoxic potential of both CP and apo‐8′ already in the concentration range of 100 nM and 1 μM, i.e. at physiologically relevant levels of β‐carotene and β‐carotene breakdown products. In contrast, no significant cytotoxic effects of these substances were observed, nor did β‐carotene induce significant cytotoxic or genotoxic effects at concentrations ranging from 0.01 up to 10 μM. However, when β‐carotene is supplemented during oxidative stress induced by hypoxia/reoxygenation, a dose‐dependent increase of CP is observed accompanied by increasing genotoxicity. Furthermore, when β‐carotene cleavage products were supplied during oxidative stress significant additional increases of genotoxic effects were observed, the additional increases indicating an additive effect of both exposures.Summarizing, these results provide strong evidence that β‐carotene breakdown products are responsible for the occurrence of carcinogenic effects found in the Alpha‐Tocopherol Beta‐carotene‐Cancer prevention (ATBC) study and the beta‐CArotene and RETinol Efficacy (CARET) Trial.
Distribution of oxidized and HNE‐modified proteins in U87 cells
Authors: Jung Tobias , Engels Martina , Kaiser Barbara , Grune Tilman 
Published: December 2008

AbstractProtein modification is one of the important processes during oxidative stress. This modification of proteins is either due to direct oxidation of proteins by various oxidants or due to secondary modification by lipid peroxidation products, e.g. 4‐hydroxynonenal. In the here presented work we compare the intracellular distribution of protein modification products after treatment of human U87 astrocytoma cells with hydrogen peroxide or HNE. The treatment with hydrogen peroxide leads mainly to a cytosolic formation of oxidized proteins whereas HNE treatment is forming HNE‐adducts throughout the cell.Therefore, we concluded that HNE diffusion distance in cells enables this lipid peroxidation product to act as a second messenger within the cell and on the other hand is the reason for the genotoxic properties of this compound.
Iron regulatory protein 1 as a sensor of reactive oxygen species
Authors: Mueller Sebastian 
Published: December 2008

AbstractIron regulatory proteins (IRP1 and 2) function as translational regulators that coordinate the cellular iron metabolism of eukaryotes by binding to the mRNA of target genes such as the transferrin receptor or ferritin. In addition to IRP2, IRP1 serves as sensor of reactive oxygen species (ROS). As iron and oxygen are essential but potentially toxic constituents of most organisms, ROS‐mediated modulation of IRP1 activity may be an important regulatory element in dissecting iron homeostasis and oxidative stress. The responses of IRP1 towards reactive oxygen species are compartment‐specific and rather complex: H2O2 activates IRP1 via a signaling cascade that leads to upregulation of the transferrin receptor and cellular iron accumulation. Contrary, superoxide inactivates IRP1 by a direct chemical attack being limited to the intracellular compartment. In particular, activation of IRP1 by H2O2 has established a new regulatory link between inflammation and iron metabolism with new clinical implications. This mechanism seems to contribute to the anemia of chronic disease and inflammation‐mediated iron accumulation in tissues. In addition, the cytotoxic side effects of redox‐cycling anticancer drugs such as doxorubicin may involve H2O2‐mediated IRP1 activation. These molecular insights open up new therapeutic strategies for the clinical management of chronic inflammation and drug‐mediated cardiotoxicity.
Effect of carotenoid oxidation products on neutrophil viability and function
Authors: Salerno C. , Crifò C. , Capuozzo E. , Sommerburg O. , Langhans C.‐D. , Siems W. 
Published: December 2008

AbstractHuman neutrophils are short‐lived cells that play important roles in host defense and acute inflammation by releasing hydrolytic and cytotoxic proteins and reactive oxygen derivatives. Apoptosis, a physiological mechanism for cell death, regulates both production and survival of neutrophils, representing a basic biological mechanism for this type of cells. Carotenoids may react with toxic oxygen metabolites released by neutrophils to form a multitude of carotenoid cleavage products that exert, in turn, relevant prooxidative biological effects. Recent data suggest that carotenoid oxidation products may affect neutrophil viability and function by exerting proapoptotic activity and interfering with superoxide production by activated cells. The prooxidant and proapoptotic activities of carotenoid oxidation products could account, at least in some cases, for the procancerogenic properties of carotenoid rich diet.
Homocysteine induces DNA synthesis and proliferation of vascular smooth muscle cells by interfering with MAPK kinase pathway
Authors: Kartal Özer Nesrin , Taha Suzan , Azzi Angelo 
Published: December 2008

AbstractHyperhomocysteinemia has been identified as an important and independent risk factor for cerebral, coronary and peripheral atherosclerosis. However the mechanisms by which homocysteine promote atherosclerotic plaque formation are not clearly defined. Earlier reports have suggested that homocysteine exert its effect via the H2O2 produced during its metabolism. To evaluate which signalling molecules are involved in homocysteine induced atherosclerotic changes during the pathogenesis of vascular diseases, we examined homocysteine induced smooth muscle cell proliferation in the presence of different signal transduction inhibitors. We show that MAPK kinase pathway is involved in homocysteine induced DNA synthesis and proliferation of vascular smooth muscle cells in the presence of the peroxide scavenging enzyme, catalase. Our data suggest that homocysteine induces smooth muscle cell growth through a pathway that is independent of H2O2, that involves MAPK kinase activation, and that results in accelerated atherosclerosis.
F2‐Isoprostanes as biomarkers of lipid peroxidation in patients with chronic renal failure
Authors: Wiswedel Ingrid , Hirsch Daniela , Carluccio Francesco , And Hannelore Hampl , Siems Werner 
Published: December 2008

AbstractChronic renal failure patients on long‐term hemolysis are found to be under increased oxidative stress, caused by antioxidant deficiency, neutrophil activation during hemodialysis (HD), platelet activation and/or chronic inflammation. Increased levels of oxidants (e.g. malondialdehyde, 4‐hydroxynonenal, hydrocarbons, lipohydroperoxides, oxycholesterols, carbonyls) in HD patients are thought to play an important role in the development of endothelial dysfunction, atherogenesis and cardiovascular disease, which is a frequent condition in end‐stage renal disease. F2‐isoprostanes have been established as chemically stable, highly specific and reliable biomarkers of in vivo oxidative stress which can very sensitively measured by gas chromatography‐mass spectrometry (Morrow et al. [17]). An up to 6‐fold increase of plasma F2‐isoprostanes in HD patients is accompanied by an enhanced formation of indicators of inflammation (e.g. C‐reactive protein) and decreases of endogenous antioxidants (e.g. ascorbate, a‐tocopherol). In their esterified form F2‐isoprostanes may be a useful criteria to evaluate the effectiveness of clinical interventions to diminish oxidant stress and associated inflammation. Furthermore, F2‐isoprostanes possess potent biological activities (e.g. 8‐iso‐PGF2α; is known as a renal vasoconstrictor) suggesting that they may also act as mediators of the cellular effects of oxidative stress and inflammation.