xCT deficiency aggravates acetaminophen-induced hepatotoxicity under inhibition of the transsulfuration pathway.

Abstract:

:Cystine, an oxidized form of cysteine (Cys), is imported into cells via the protein xCT, which is also associated with the export of glutamate as the counter amino acid. In the current study, we attempted to rationalize roles of xCT in the livers of male mice. While xCT was not expressed in the livers of ordinary mice, it was induced under conditions of glutathione depletion, caused by the administration of acetaminophen (AAP). To differentiate the role between xCT and the transsulfuration pathway on the supply of Cys, we employed an inhibitor of the enzyme cystathionine γ-lyase, propargylglycine (PPG). This inhibitor caused a marked aggravation in AAP-induced hepatic damage and the mortality of the xCT-/- mice was increased to a greater extent than that for the xCT+/+ mice. While a PPG pretreatment had no effect on liver condition or Cys levels, the administration of AAP to the PPG-pretreated mice reduced the levels of Cys as well as glutathione to very low levels in both the xCT+/+ and xCT-/- mice. These findings indicate that the transsulfuration pathway plays a major role in replenishing Cys when glutathione levels are low. Moreover, an ascorbic acid insufficiency, induced by Akr1a ablation, further aggravated the AAP-induced liver damage in the case of the xCT deficiency, indicating that glutathione and ascorbic acid function cooperatively in protecting the liver. In conclusion, while the transsulfuration pathway plays a primary role in supplying Cys to the redox system in the liver, xCT is induced in cases of emergencies, by compensating for Cys supply systems.

journal_name

Free Radic Res

journal_title

Free radical research

authors

Kang ES,Lee J,Homma T,Kurahashi T,Kobayashi S,Nabeshima A,Yamada S,Seo HG,Miyata S,Sato H,Fujii J

doi

10.1080/10715762.2017.1282157

subject

Has Abstract

pub_date

2017-01-01 00:00:00

pages

80-90

issue

1

eissn

1071-5762

issn

1029-2470

journal_volume

51

pub_type

杂志文章
  • Podophyllotoxin and rutin in combination prevents oxidative stress mediated cell death and advances revival of mice gastrointestine following lethal radiation injury.

    abstract::Intestinal injury is inevitable during exposure to high radiation doses and is a common side effect observed during abdominal/pelvic radiotherapy. Yet, no radiation countermeasures are available for gastrointestine (GI) injury management. The aim of this study is to determine the effects of podophyllotoxin and rutin i...

    journal_title:Free radical research

    pub_type: 杂志文章

    doi:10.1080/10715762.2017.1418982

    authors: Dutta A,Gupta ML,Verma S

    更新日期:2018-01-01 00:00:00

  • APE1/Ref-1 regulates PTEN expression mediated by Egr-1.

    abstract::APE1/Ref-1, the mammalian ortholog of E. coli Xth, and a multifunctional protein possessing both DNA repair and transcriptional regulatory activities, has dual role in controlling cellular response to oxidative stress. It is rate-limiting in repair of oxidative DNA damage including strand breaks and also has co-transc...

    journal_title:Free radical research

    pub_type: 杂志文章

    doi:10.1080/10715760701765616

    authors: Fantini D,Vascotto C,Deganuto M,Bivi N,Gustincich S,Marcon G,Quadrifoglio F,Damante G,Bhakat KK,Mitra S,Tell G

    更新日期:2008-01-01 00:00:00

  • pLG72 induces superoxide radicals via interaction and aggregation with SOD1.

    abstract::G72 has been characterised as a susceptibility gene that can have wide-ranging effects in a number of neurodegenerative diseases, including schizophrenia and major depression. Indeed, its product, pLG72, is a potential serum biomarker for schizophrenia. Previous transcriptomic and biochemical studies have indicated th...

    journal_title:Free radical research

    pub_type: 杂志文章

    doi:10.1080/10715762.2018.1504293

    authors: Wang M,Saw HP,Cui FF,Lin SY,Chang HT,Chiu CD

    更新日期:2018-09-01 00:00:00

  • a-Tocopherol Content and a-Tocopherol Transfer Protein Expression in Leukocytes of Children with Acute Leukemia.

    abstract::α-Tocopherol (a form of vitamin E) is a fat-soluble vitamin that can prevent lipid peroxidation of cell membranes. This antioxidant activity of α-tocopherol can help to prevent cardiovascular disease, atherosclerosis and cancer. We investigated the α-tocopherol level and the expression of α-tocopherol transfer protein...

    journal_title:Free radical research

    pub_type: 杂志文章

    doi:10.1080/10715760310001600426

    authors: Misaki K,Takitani K,Ogihara T,Inoue A,Kawakami C,Kuno T,Kawamura N,Miyake M,Nakagawa T,Tamai H

    更新日期:2003-01-01 00:00:00

  • Pathological aspects of lipid peroxidation.

    abstract::Lipid peroxidation (LPO) product accumulation in human tissues is a major cause of tissular and cellular dysfunction that plays a major role in ageing and most age-related and oxidative stress-related diseases. The current evidence for the implication of LPO in pathological processes is discussed in this review. New d...

    journal_title:Free radical research

    pub_type: 杂志文章,评审

    doi:10.3109/10715762.2010.498478

    authors: Negre-Salvayre A,Auge N,Ayala V,Basaga H,Boada J,Brenke R,Chapple S,Cohen G,Feher J,Grune T,Lengyel G,Mann GE,Pamplona R,Poli G,Portero-Otin M,Riahi Y,Salvayre R,Sasson S,Serrano J,Shamni O,Siems W,Siow RC,Wis

    更新日期:2010-10-01 00:00:00

  • A free radical initiator, 2,2'-azobis (2-aminopropane) dihydrochloride enhances hyperthermia-induced apoptosis in human uterine cervical cancer cell lines.

    abstract::Hyperthermia-induced apoptosis and its enhancement in the presence of a temperature-dependent free radical initiator, 2,2'-azobis (2-aminopropane) dihydrochloride (AAPH) were examined in human uterine cervical cancer cell lines, CaSki and HeLa. When both cell lines were treated with hyperthermia at 44 degrees C for 60...

    journal_title:Free radical research

    pub_type: 杂志文章

    doi:10.1080/1071576031000088292

    authors: Yuki H,Kondo T,Zhao QL,Fujiwara Y,Tanabe K,Ogawa R,Nakashima A,Fushiki H,Fujimura M,Saito S

    更新日期:2003-06-01 00:00:00

  • Antisteroidogenic effects of hydrogen peroxide on rat granulosa cells.

    abstract::Rat granulosa cells (GCs) were treated with human chorionic gonadotropin (hCG), 8-bromo-adenosine 3',5'-cyclic monophosphate (8-Br-cAMP), forskolin, phorbol 12-myristate 13-acetate (PMA), A23187 or pregnenolone in the absence or presence of hydrogen peroxide (H(2)O(2)). Different doses of trilostane were applied to GC...

    journal_title:Free radical research

    pub_type: 杂志文章

    doi:10.3109/10715762.2012.669835

    authors: Yu PL,Lin TM,Wang SW,Wang PS

    更新日期:2012-06-01 00:00:00

  • Recombinant human thioredoxin-1 becomes oxidized in circulation and suppresses bleomycin-induced neutrophil recruitment in the rat airway.

    abstract::Thioredoxin-1 (TRX) is a redox-active protein with anti-inflammatory effects. This study investigated the optimal delivery method and the mechanisms of recombinant human TRX (rhTRX) to suppress neutrophil recruitment in a rat bleomycin (BLM)-induced sustained acute lung injury model. In male Wister rats intratracheall...

    journal_title:Free radical research

    pub_type: 杂志文章

    doi:10.1080/10715760701487682

    authors: Nakamura T,Hoshino Y,Yamada A,Teratani A,Furukawa S,Okuyama H,Ueda S,Wada H,Yodoi J,Nakamura H

    更新日期:2007-10-01 00:00:00

  • Attenuation of oxidative hemolysis of human red blood cells by the natural phenolic compound, allylpyrocatechol.

    abstract::The protecting ability of the Piper betle leaves-derived phenol, allylpyrocatechol (APC) against AAPH-induced membrane damage of human red blood cells (RBCs) was investigated. Compared to control, AAPH (50 mM) treatment resulted in significant hemolysis (55%, p < 0.01), associated with increased malondialdehyde (MDA) ...

    journal_title:Free radical research

    pub_type: 杂志文章

    doi:10.3109/10715762.2013.816847

    authors: Iyer MK,Nayak R,Colah R,Chattopadhyay S

    更新日期:2013-09-01 00:00:00

  • Curcumin prevents maleate-induced nephrotoxicity: relation to hemodynamic alterations, oxidative stress, mitochondrial oxygen consumption and activity of respiratory complex I.

    abstract::The potential protective effect of the dietary antioxidant curcumin (120 mg/Kg/day for 6 days) against the renal injury induced by maleate was evaluated. Tubular proteinuria and oxidative stress were induced by a single injection of maleate (400 mg/kg) in rats. Maleate-induced renal injury included increase in renal v...

    journal_title:Free radical research

    pub_type: 杂志文章

    doi:10.3109/10715762.2014.954109

    authors: Tapia E,Sánchez-Lozada LG,García-Niño WR,García E,Cerecedo A,García-Arroyo FE,Osorio H,Arellano A,Cristóbal-García M,Loredo ML,Molina-Jijón E,Hernández-Damián J,Negrette-Guzmán M,Zazueta C,Huerta-Yepez S,Reyes JL,Madero M

    更新日期:2014-11-01 00:00:00

  • Increase in insulin-induced relaxation of consecutive arterial segments toward the periphery: Role of vascular oxidative state.

    abstract:RATIONALE:The oxidative state has been implicated in the signaling of various vasomotor functions, yet its role regarding the vasomotor action of insulin is less known. OBJECTIVE:To investigate the insulin-evoked relaxations of consecutive arterial segments of different oxidative state and the role of extracellular si...

    journal_title:Free radical research

    pub_type: 杂志文章

    doi:10.3109/10715762.2014.904507

    authors: Szijártó IA,Molnár GA,Mikolás E,Fisi V,Laczy B,Gollasch M,Koller A,Wittmann I

    更新日期:2014-07-01 00:00:00

  • Resveratrol treatment protects against doxorubicin-induced cardiotoxicity by alleviating oxidative damage.

    abstract::The possible protective effects of resveratrol (RVT) against cardiotoxicity were investigated in Wistar albino rats treated with saline, saline+doxorubicin (DOX; 20 mg/kg) or RVT (10 mg/kg)+DOX. Blood pressure and heart rate were recorded on the 1st week and on the 7th week, while cardiomyopathy was assessed using tra...

    journal_title:Free radical research

    pub_type: 杂志文章

    doi:10.1080/10715760802673008

    authors: Tatlidede E,Sehirli O,Velioğlu-Oğünc A,Cetinel S,Yeğen BC,Yarat A,Süleymanoğlu S,Sener G

    更新日期:2009-03-01 00:00:00

  • Scavenging of benzylperoxyl radicals by carotenoids.

    abstract::Carotenoids scavenge simple lipid-like alkylperoxyl radicals. However, the rate constant is too low to be determined directly and the mechanism is likewise not known with certainty [Mortensen, A. and Skibsted, L.H. (1998) FEBS Lett. 426, 392-396]. It is demonstrated that carotenoids react with peroxyl radicals only sl...

    journal_title:Free radical research

    pub_type: 杂志文章

    doi:10.1080/10715760290006501

    authors: Mortensen A

    更新日期:2002-02-01 00:00:00

  • Free radicals in irradiated drugs: an EPR study.

    abstract::Exposure of dry powder forms of the drugs nitrendipine, nifedipine, felodipine, and nimodipine to gamma-radiation results in the formation of free radicals detected by electron paramagnetic resonance (EPR) spectroscopy. The four structurally related drugs show qualitatively identical EPR spectral features in terms of ...

    journal_title:Free radical research

    pub_type: 杂志文章

    doi:10.1080/10715769900300791

    authors: Taiwo FA,Patterson LH,Jaroszkiewicz E,Marciniec B,Ogrodowczyk M

    更新日期:1999-09-01 00:00:00

  • Antioxidative effects of fluvastatin and its metabolites against oxidative DNA damage in mammalian cultured cells.

    abstract::We investigated the effects of fluvastatin, a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor, on reactive oxygen species (ROS) and on oxidative DNA damage in vitro, as well as the effects of the main fluvastatin metabolites (M2, M3, and M4) and other inhibitors of the same enzyme, pravastatin and simvastati...

    journal_title:Free radical research

    pub_type: 杂志文章

    doi:10.1080/10715760100301291

    authors: Imaeda A,Tanigawa T,Aoki T,Kondo Y,Nakamura N,Yoshikawa T

    更新日期:2001-12-01 00:00:00

  • Adaptation to multiday ozone exposure is associated with a sustained increase of bronchoalveolar uric acid.

    abstract::The phenomenon of ozone tolerance is described, but the underlying mechanisms remain unknown. We tested whether adaptation to multiday ozone exposure was related to an upregulated pulmonary antioxidant defence. Six calves were exposed to 0.75 ppm ozone, 12 h day(-1) for seven consecutive days. Pulmonary function tests...

    journal_title:Free radical research

    pub_type: 杂志文章

    doi:10.1080/10715760210169

    authors: Kirschvink N,Fiévez L,Bureau F,Degand G,Maghuin-Rogister G,Smith N,Art T,Lekeux P

    更新日期:2002-01-01 00:00:00

  • Comparison of LDL trap assay to other tests of antioxidant capacity; effect of vitamin E and lovastatin treatment.

    abstract::Oxidized low density lipoprotein (LDL) has a major impact in the development of atherosclerosis. Risk for oxidative modification of LDL is usually determined indirectly by measuring the capability of LDL to resist radical insult. We compared three different methods quantifying the antioxidative capacity of LDL ex vivo...

    journal_title:Free radical research

    pub_type: 临床试验,杂志文章

    doi:10.1080/10715760000301111

    authors: Malminiemi K,Palomäki A,Malminiemi O

    更新日期:2000-11-01 00:00:00

  • A validated method for rapid analysis of ethane in breath and its application in kinetic studies in human volunteers.

    abstract::Oxidative stress may initiate lipid peroxidation that generates ethane. Ethane, at low concentrations, is eliminated by pulmonary exhalation. Previous methods have not allowed frequent sampling, thus ethane kinetics has not been studied in man. A validated method over the range 3.8-100,000 ppb with a limit of quantita...

    journal_title:Free radical research

    pub_type: 杂志文章

    doi:10.1080/1071576031000107353

    authors: Dale O,Bergum H,Lund T,Nilsen T,Aadahl P,Stenseth R

    更新日期:2003-08-01 00:00:00

  • Quinolinic aminoxyl protects albumin against peroxyl radical mediated damage.

    abstract::A study of peroxyl radical-mediated bovine serum albumin oxidation in the presence of the quinolinic aminoxyl 1,2-dihydro-2,2-diphenyl-4-ethoxy-quinoline-1-oxyl (QAO) was carried out in order to test its efficiency as a protein antioxidant. Albumin oxidation was induced by the tert-butylhydroperoxide/PbO2 system. The ...

    journal_title:Free radical research

    pub_type: 杂志文章

    doi:10.3109/10715769409056583

    authors: Tanfani F,Carloni P,Damiani E,Greci L,Wozniak M,Kulawiak D,Jankowski K,Kaczor J,Matuszkiewics A

    更新日期:1994-10-01 00:00:00

  • Effect of rhinovirus challenge on antioxidant enzymes in respiratory epithelial cells.

    abstract::The host inflammatory response appears to be an important contributor to the pathogenesis of human viral respiratory illness. Virus-induced oxidative stress appears to mediate an early phase of elaboration of the proinflammatory cytokine interleukin-8 by respiratory epithelial cells. The purpose of these studies was t...

    journal_title:Free radical research

    pub_type: 杂志文章

    doi:10.1080/1071576021000028316

    authors: Kaul P,Singh I,Turner RB

    更新日期:2002-10-01 00:00:00

  • Hydrazyl-nitrones, novel hybrid molecules in free radical research.

    abstract::This work describes the synthesis and characterisation of some novel hybrid molecules which contains in the same molecule a free radical moiety of hydrazyl type and a spin-trap moiety of nitrone type. The new compounds synthesized have multiple and easy to follow spectroscopic properties, making them useful as sensors...

    journal_title:Free radical research

    pub_type: 杂志文章

    doi:10.1080/10715760500385699

    authors: Ionita P

    更新日期:2006-01-01 00:00:00

  • Effect of β-carotene on catechol-induced genotoxicity in vitro: evidence of both enhanced and reduced DNA damage.

    abstract::Intake of antioxidants from the diet has been recognized to have beneficial health effects, but the potential benefit of taking antioxidants such as β-carotene as supplements is controversial. The aim of the present study was to evaluate the potential protective effects of a physiologically relevant concentration (2 μ...

    journal_title:Free radical research

    pub_type: 杂志文章

    doi:10.3109/10715762.2013.815346

    authors: Åsgård R,Hellman B

    更新日期:2013-09-01 00:00:00

  • Associations between oxidative parameters in pregnancy and birth anthropometry in a cohort of women and children in rural Bangladesh: the MINIMat-cohort.

    abstract::Oxidative stress is suggested as a potential mechanism in impaired foetal growth, smaller birth size and thus subsequently adult chronic diseases. We have investigated associations between oxidative stress in pregnancy and birth anthropometry (weight, height, head and chest circumferences). In the MINIMat-trial (Mater...

    journal_title:Free radical research

    pub_type: 临床试验,杂志文章

    doi:10.3109/10715762.2011.651467

    authors: Lindström E,Persson LÅ,Raqib R,El Arifeen S,Basu S,Ekström EC

    更新日期:2012-03-01 00:00:00

  • Effects of an oxidizing agent (hydrogen peroxide) on the glutathione system in epidermal cells of Allium cepa L. investigated by histochemical staining.

    abstract::The glutathione system in epidermal cells of Allium cepa L. was measured by a quantitative image analysis method, using histochemical staining by monochlorobimane. Blockage of thiol groups with N-ethylmaleimide decreased fluorescence to a small rest fluorescence of maximum 5%. Pre-treatment with dithiothreitol increas...

    journal_title:Free radical research

    pub_type: 杂志文章

    doi:10.1080/10715769900301411

    authors: Müller M,Tausz M,Wonisch A,Grill D

    更新日期:1999-12-01 00:00:00

  • Endogenous and dietary indoles: a class of antioxidants and radical scavengers in the ABTS assay.

    abstract::Indoles are very common in the body and diet and participate in many biochemical processes. A total of twenty-nine indoles and analogs were examined for their properties as antioxidants and radical scavengers against 2,2'-Azino-bis(3-ethylbenzthiazoline-6-sulfonic acid) ABTS*+ radical cation. With only a few exception...

    journal_title:Free radical research

    pub_type: 杂志文章

    doi:10.1080/10611860310001648167

    authors: Herraiz T,Galisteo J

    更新日期:2004-03-01 00:00:00

  • The role of free radicals in paraquat-induced corneal lesions.

    abstract::Paraquat is a synthetic bipyridylium salt widely used as herbicide and defoliant. Enzyme-catalyzed redoxcycling of paraquat generates oxygen radicals. The toxic, even lethal, effects of paraquat are due to free radical-mediated tissue injury. Ocular lesions, sometimes quite severe, have been observed following acciden...

    journal_title:Free radical research

    pub_type: 杂志文章

    doi:10.3109/10715769509064020

    authors: Nordquist RE,Nguyen H,Poyer JL,Carubelli R

    更新日期:1995-07-01 00:00:00

  • Mechanism of the anti-hypertensive property of the naturally occurring phenolic, malabaricone C in DOCA-salt rats.

    abstract::In this study, we studied whether chronic oral administration of the natural antioxidant, malabaricone C (mal C) can reduce blood pressure (BP) and attenuate cardio-vascular remodeling in deoxycorticosterone acetate (DOCA)-salt hypertensive rats. The dose of mal C for its anti-hypertensive action was optimized by meas...

    journal_title:Free radical research

    pub_type: 杂志文章

    doi:10.3109/10715762.2015.1112005

    authors: Rathee JS,Patro BS,Brown L,Chattopadhyay S

    更新日期:2016-01-01 00:00:00

  • Low oxygen tension alleviates oxidative damage and delays cellular senescence in G6PD-deficient cells.

    abstract::Previous studies have shown that glucose-6-phosphate dehydrogenase (G6PD)-deficient cells are under increased oxidative stress and undergo premature cellular senescence. The present study demonstrates that G6PD-deficient cells cultured under 3% oxygen concentration had an extended replicative lifespan, as compared wit...

    journal_title:Free radical research

    pub_type: 杂志文章

    doi:10.1080/10715760601184819

    authors: Ho HY,Cheng ML,Cheng PF,Chiu DT

    更新日期:2007-05-01 00:00:00

  • Edaravone inhibits rheumatoid synovial cell proliferation and migration.

    abstract::Rheumatoid arthritis (RA) is characterized by synovial proliferation and migration which is induced by proinflammatory cytokines or oxidative stress, followed by joint destruction. Edaravone, clinically available free radical scavenger in Japan, is confirmed to be beneficial in the acute stage of cerebral infarction. ...

    journal_title:Free radical research

    pub_type: 杂志文章

    doi:10.1080/10715760500401116

    authors: Arii K,Kumon Y,Ikeda Y,Suehiro T,Hashimoto K

    更新日期:2006-02-01 00:00:00

  • Ceruloplasmin decreases respiratory burst reaction during pregnancy.

    abstract::Testing of pregnant women reveals weakening of neutrophil-mediated effector functions, such as reactive oxygen species generation. This study provides data confirming the phenomenon, gained through application of the flow cytometry technique. Key factors influencing neutrophil functional activity in blood plasma of pr...

    journal_title:Free radical research

    pub_type: 杂志文章

    doi:10.1080/10715762.2016.1197395

    authors: Varfolomeeva EY,Semenova EV,Sokolov AV,Aplin KD,Timofeeva KE,Vasilyev VB,Filatov MV

    更新日期:2016-08-01 00:00:00