Hydrogen peroxide-mediated neuronal cell death induced by an endogenous neurotoxin, 3-hydroxykynurenine.

Abstract:

:3-Hydroxykynurenine (3-HK) is a tryptophan metabolite whose level in the brain is markedly elevated under several pathological conditions, including Huntington disease and human immunodeficiency virus infection. Here we demonstrate that micromolar concentrations (1-100 microM) of 3-HK cause cell death in primary neuronal cultures prepared from rat striatum. The neurotoxicity of 3-HK was blocked by catalase and desferrioxamine but not by superoxide dismutase, indicating that the generation of hydrogen peroxide and hydroxyl radical is involved in the toxicity. Measurement of peroxide levels revealed that 3-HK caused intracellular accumulation of peroxide, which was largely attenuated by application of catalase. The peroxide accumulation and cell death caused by 1-10 microM 3-HK were also blocked by pretreatment with allopurinol or oxypurinol, suggesting that endogenous xanthine oxidase activity is involved in exacerbation of 3-HK neurotoxicity. Furthermore, NADPH diaphorase-containing neurons were spared from toxicity of these concentrations of 3-HK, a finding reminiscent of the pathological characteristics of several neurodegenerative disorders such as Huntington disease. These results suggest that 3-HK at pathologically relevant concentrations renders neuronal cells subject to oxidative stress leading to cell death, and therefore that this endogenous compound should be regarded as an important factor in pathogenesis of neurodegenerative disorders.

authors

Okuda S,Nishiyama N,Saito H,Katsuki H

doi

10.1073/pnas.93.22.12553

subject

Has Abstract

pub_date

1996-10-29 00:00:00

pages

12553-8

issue

22

eissn

0027-8424

issn

1091-6490

journal_volume

93

pub_type

杂志文章
  • FERONIA receptor-like kinase regulates RHO GTPase signaling of root hair development.

    abstract::Plant RHO GTPases (RAC/ROPs) mediate multiple extracellular signals ranging from hormone to stress and regulate diverse cellular processes important for polarized cell growth, differentiation, development, reproduction, and responses to the environment. They shuttle between the GDP-bound inactive state and the GTP-bou...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1005366107

    authors: Duan Q,Kita D,Li C,Cheung AY,Wu HM

    更新日期:2010-10-12 00:00:00

  • Mitochondrial pathology and muscle and dopaminergic neuron degeneration caused by inactivation of Drosophila Pink1 is rescued by Parkin.

    abstract::Mutations in Pink1, a gene encoding a Ser/Thr kinase with a mitochondrial-targeting signal, are associated with Parkinson's disease (PD), the most common movement disorder characterized by selective loss of dopaminergic neurons. The mechanism by which loss of Pink1 leads to neurodegeneration is not understood. Here we...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.0602493103

    authors: Yang Y,Gehrke S,Imai Y,Huang Z,Ouyang Y,Wang JW,Yang L,Beal MF,Vogel H,Lu B

    更新日期:2006-07-11 00:00:00

  • Accumulation of PNPLA3 on lipid droplets is the basis of associated hepatic steatosis.

    abstract::Fatty liver disease (FLD) is a disorder in which accumulation of triglycerides (TGs) in the liver can lead to inflammation, fibrosis, and cirrhosis. Previously, we identified a variant (I148M) in patatin-like phospholipase domain-containing protein 3 (PNPLA3) that is strongly associated with FLD, but the mechanistic b...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1901974116

    authors: BasuRay S,Wang Y,Smagris E,Cohen JC,Hobbs HH

    更新日期:2019-05-07 00:00:00

  • Intrathymic maturation of murine T lymphocytes from CD8+ precursors.

    abstract::The CD4-8- thymocyte subset contains immature precursors for phenotypically and functionally mature CD4+8- and CD4-8+ thymocytes and peripheral T cells, as well as nonmature CD4+8+ thymocytes, most of which die in situ. The intrathymic death of most thymocytes is probably related to selective influences that ensure th...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.86.19.7542

    authors: Guidos CJ,Weissman IL,Adkins B

    更新日期:1989-10-01 00:00:00

  • Wetting morphologies at microstructured surfaces.

    abstract::The wetting of microstructured surfaces is studied both experimentally and theoretically. Even relatively simple surface topographies such as grooves with rectangular cross section exhibit a large variety of different wetting morphologies as observed by atomic force microscopy. This polymorphism arises from liquid wed...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.0407721102

    authors: Seemann R,Brinkmann M,Kramer EJ,Lange FF,Lipowsky R

    更新日期:2005-02-08 00:00:00

  • Requirement of proteins S5 and S9 from 30S subunits for the ribosome-dependent GTPase activity of elongation factor G.

    abstract::During CsCl isopycnic centrifugation at 20 mM Mg(++), Escherichia coli 30S ribosomal subunits specifically lose proteins S1, S2, S3, S5, S9, S10, and S14. The resultant 30S core is unable to stimulate the GTPase activity of EF-G in the presence of 50S subunits. Activity could be restored to a small extent by adding ba...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.70.1.151

    authors: Marsh RC,Parmeggiani A

    更新日期:1973-01-01 00:00:00

  • Kinetics of hydrogen bond breakage in the process of unfolding of ribonuclease A measured by pulsed hydrogen exchange.

    abstract::A sensitive test for kinetic unfolding intermediates in ribonuclease A (EC 3.1.27.5) is performed under conditions where the enzyme unfolds slowly (10 degrees C, pH 8.0, 4.5 M guanidinium chloride). Exchange of peptide NH protons (2H-1H) is used to monitor structural opening of individual hydrogen bonds during unfoldi...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.92.7.2657

    authors: Kiefhaber T,Baldwin RL

    更新日期:1995-03-28 00:00:00

  • Vaccines, new opportunities for a new society.

    abstract::Vaccination is the most effective medical intervention ever introduced and, together with clean water and sanitation, it has eliminated a large part of the infectious diseases that once killed millions of people. A recent study concluded that since 1924 in the United States alone, vaccines have prevented 40 million ca...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章,评审

    doi:10.1073/pnas.1402981111

    authors: Rappuoli R,Pizza M,Del Giudice G,De Gregorio E

    更新日期:2014-08-26 00:00:00

  • Benthic invaders control the phosphorus cycle in the world's largest freshwater ecosystem.

    abstract::The productivity of aquatic ecosystems depends on the supply of limiting nutrients. The invasion of the Laurentian Great Lakes, the world's largest freshwater ecosystem, by dreissenid (zebra and quagga) mussels has dramatically altered the ecology of these lakes. A key open question is how dreissenids affect the cycli...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.2008223118

    authors: Li J,Ianaiev V,Huff A,Zalusky J,Ozersky T,Katsev S

    更新日期:2021-02-09 00:00:00

  • Opioid receptor reserve in normal and morphine-tolerant guinea pig ileum myenteric plexus.

    abstract::We have measured the opioid receptor reserve in the guinea pig ileum myenteric plexus by means of the site-directed alkylating agent, beta-chlornaltrexamine. Treatment of the tissue with low (less than 10 nM) concentrations of beta-chlornaltrexamine caused a parallel shift of the log concentration-response curves for ...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.81.22.7253

    authors: Chavkin C,Goldstein A

    更新日期:1984-11-01 00:00:00

  • The 90-kDa component of reticulocyte heme-regulated eIF-2 alpha (initiation factor 2 alpha-subunit) kinase is derived from the beta subunit of spectrin.

    abstract::Antibodies from three different lines of monoclonal hybridomas crossreact with both the beta subunit of spectrin and the 90-kDa peptide present in highly purified preparations of the heme-controlled eIF-2 alpha (initiation factor 2 alpha-subunit) kinase from rabbit reticulocytes. Antibodies from two of the three lines...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.82.16.5332

    authors: Kudlicki W,Fullilove S,Kramer G,Hardesty B

    更新日期:1985-08-01 00:00:00

  • The cellular ecology of progressive neoplastic transformation: a clonal analysis.

    abstract::A comparison was made of the competence for neoplastic transformation in three different sublines of NIH 3T3 cells and multiple clonal derivatives of each. Over 90% of the neoplastic foci produced by an uncloned transformed (t-SA') subline on a confluent background of nontransformed cells were of the dense, multilayer...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.96.5.2093

    authors: Chow M,Rubin H

    更新日期:1999-03-02 00:00:00

  • Reducing the number of inferior treatments in clinical trials.

    abstract::In clinical trials comparing two treatments, one would often like to control the probability of erroneous decision while minimizing not the total sample size but the number of patients given the inferior treatment. To do this obviously requires that one use a datadependent allocation rule for the two treatments rather...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 临床试验,杂志文章

    doi:10.1073/pnas.69.10.2993

    authors: Flehinger BJ,Louis TA,Robbins H,Singer BH

    更新日期:1972-10-01 00:00:00

  • Mechanisms of acute axonal degeneration in the optic nerve in vivo.

    abstract::Axonal degeneration is an initial key step in traumatic and neurodegenerative CNS disorders. We established a unique in vivo epifluorescence imaging paradigm to characterize very early events in axonal degeneration in the rat optic nerve. Single retinal ganglion cell axons were visualized by AAV-mediated expression of...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.0909794107

    authors: Knöferle J,Koch JC,Ostendorf T,Michel U,Planchamp V,Vutova P,Tönges L,Stadelmann C,Brück W,Bähr M,Lingor P

    更新日期:2010-03-30 00:00:00

  • DNA strand-specific repair of (+-)-3 alpha,4 beta-dihydroxy-1 alpha,2 alpha-epoxy-1,2,3,4-tetrahydrobenzo[c]phenanthrene adducts in the hamster dihydrofolate reductase gene.

    abstract::We evaluated the formation and removal of (+-)-3 alpha,4 beta-dihydroxy-1 alpha,2 alpha-epoxy-1,2,3,4- tetrahydrobenzo[c]phenanthrene (BcPHDE)-DNA adducts in two Chinese hamster ovary (CHO) cell lines. One line of repair-proficient cells (MK42) carries a stable 150-fold amplification of the dihydrofolate reductase (DH...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.89.24.11925

    authors: Carothers AM,Zhen W,Mucha J,Zhang YJ,Santella RM,Grunberger D,Bohr VA

    更新日期:1992-12-15 00:00:00

  • Enhancing the antitumor efficacy of a cell-surface death ligand by covalent membrane display.

    abstract::TNF superfamily death ligands are expressed on the surface of immune cells and can trigger apoptosis in susceptible cancer cells by engaging cognate death receptors. A recombinant soluble protein comprising the ectodomain of Apo2 ligand/TNF-related apoptosis-inducing ligand (Apo2L/TRAIL) has shown remarkable preclinic...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1418962112

    authors: Nair PM,Flores H,Gogineni A,Marsters S,Lawrence DA,Kelley RF,Ngu H,Sagolla M,Komuves L,Bourgon R,Settleman J,Ashkenazi A

    更新日期:2015-05-05 00:00:00

  • Optimizing transmembrane domain helicity accelerates insulin receptor internalization and lateral mobility.

    abstract::Transmembrane (TM) domains of integral membrane proteins are generally thought to be helical. However, a Gly-Pro sequence within the TM domain of the insulin receptor is predicted to act as a helix breaker. CD analyses of model TM peptides in a lipid-like environment show that substitution of Gly and Pro by Ala enhanc...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.90.12.5762

    authors: Goncalves E,Yamada K,Thatte HS,Backer JM,Golan DE,Kahn CR,Shoelson SE

    更新日期:1993-06-15 00:00:00

  • How the Dorsal gradient works: insights from postgenome technologies.

    abstract::Gradients of extracellular signaling molecules and transcription factors are used in a variety of developmental processes, including the patterning of the Drosophila embryo, the establishment of diverse neuronal cell types in the vertebrate neural tube, and the anterior-posterior patterning of vertebrate limbs. Here, ...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章,评审

    doi:10.1073/pnas.0806476105

    authors: Hong JW,Hendrix DA,Papatsenko D,Levine MS

    更新日期:2008-12-23 00:00:00

  • Dosage compensation for enzyme activities in Drosophila melanogaster.

    abstract::There are certain genes on the sex chromosome of Drosophila for which the female contains twice as many copies as the male. Some of the genes in this group produce the same phenotype in each sex despite the dosage difference and are said, therefore, to manifest dosage compensation. The structural genes for glucose-6-p...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.62.2.528

    authors: Seecof RL,Kaplan WD,Futch DG

    更新日期:1969-02-01 00:00:00

  • Complete nucleotide sequence of the gene for the specific glycoprotein (gp55) of Friend spleen focus-forming virus.

    abstract::The complete nucleotide sequence of the gene for the specific glycoprotein (gp55) of the polycythemic strain of Friend spleen focus-forming virus (SFFV) was derived from the cloned SFFV DNA intermediate. The gp55 gene is present within 1.4 kilobases of the 5' side of the 3'long terminal repeat sequence. The open readi...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.80.13.3913

    authors: Amanuma H,Katori A,Obata M,Sagata N,Ikawa Y

    更新日期:1983-07-01 00:00:00

  • Ultrastructural localization of tyrosine hydroxylase in noradrenergic neurons of brain.

    abstract::Tyrosine hydroxylase (EC 1.14.16.2), the enzyme catalyzing the rate-limiting step in catecholamine biosynthesis, was localized by electron microscopy within noradrenergic neurons of the nucleus locus coeruleus of the rat brain with a specific antibody to tyrosine hydroxylase labeled by the peroxidase-antiperoxidase im...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.72.2.659

    authors: Pickel VM,Joh TH,Reis DJ

    更新日期:1975-02-01 00:00:00

  • Molecular characterization of five human anti-human immunodeficiency virus type 1 antibody heavy chains reveals extensive somatic mutation typical of an antigen-driven immune response.

    abstract::We report the heavy chain variable region sequences from the cDNAs of five previously described monoclonal cell lines producing human antibodies specific for the human immunodeficiency virus type 1 and detail the molecular characteristics, germ-line origins, and extent of somatic mutation among these antibodies. Three...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.88.17.7783

    authors: Andris JS,Johnson S,Zolla-Pazner S,Capra JD

    更新日期:1991-09-01 00:00:00

  • SRC-2 orchestrates polygenic inputs for fine-tuning glucose homeostasis.

    abstract::Despite extensive efforts to understand the monogenic contributions to perturbed glucose homeostasis, the complexity of genetic events that fractionally contribute to the spectrum of this pathology remain poorly understood. Proper maintenance of glucose homeostasis is the central feature of a constellation of comorbid...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1519073112

    authors: Fleet T,Zhang B,Lin F,Zhu B,Dasgupta S,Stashi E,Tackett B,Thevananther S,Rajapakshe KI,Gonzales N,Dean A,Mao J,Timchenko N,Malovannaya A,Qin J,Coarfa C,DeMayo F,Dacso CC,Foulds CE,O'Malley BW,York B

    更新日期:2015-11-03 00:00:00

  • A digital media literacy intervention increases discernment between mainstream and false news in the United States and India.

    abstract::Widespread belief in misinformation circulating online is a critical challenge for modern societies. While research to date has focused on psychological and political antecedents to this phenomenon, few studies have explored the role of digital media literacy shortfalls. Using data from preregistered survey experiment...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1920498117

    authors: Guess AM,Lerner M,Lyons B,Montgomery JM,Nyhan B,Reifler J,Sircar N

    更新日期:2020-07-07 00:00:00

  • Control of chondrogenic expression in mesodermal cells of embryonic chick limb.

    abstract::Chick-limb mesodermal cells have been maintained in tissue culture under conditions that permit development of muscle and cartilage. 3-Acetylpyridine, a nicotinamide-antagonized muscle teratogen, potentiates chondrogenic expression in cell cultures, as evidenced by histological and biochemical criteria, including the ...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.70.6.1713

    authors: Caplan AI,Stoolmiller AC

    更新日期:1973-06-01 00:00:00

  • Poly(ADP-ribose) glycohydrolase mediates oxidative and excitotoxic neuronal death.

    abstract::Excessive activation of poly(ADP-ribose) polymerase 1 (PARP1) leads to NAD(+) depletion and cell death during ischemia and other conditions that generate extensive DNA damage. When activated by DNA strand breaks, PARP1 uses NAD(+) as substrate to form ADP-ribose polymers on specific acceptor proteins. These polymers a...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.211202598

    authors: Ying W,Sevigny MB,Chen Y,Swanson RA

    更新日期:2001-10-09 00:00:00

  • Polyglutamine-expanded ataxin-7 inhibits STAGA histone acetyltransferase activity to produce retinal degeneration.

    abstract::Spinocerebellar ataxia type 7 (SCA7) is characterized by cone-rod dystrophy retinal degeneration and is caused by a polyglutamine [poly(Q)] expansion within ataxin-7, a protein of previously unknown function. Here, we report that ataxin-7 is an integral component of the mammalian STAGA (SPT3-TAF9-ADA-GCN5 acetyltransf...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.0503505102

    authors: Palhan VB,Chen S,Peng GH,Tjernberg A,Gamper AM,Fan Y,Chait BT,La Spada AR,Roeder RG

    更新日期:2005-06-14 00:00:00

  • Integration of epigenetic and genetic controls of seed size by cytokinin in Arabidopsis.

    abstract::The development of seeds in flowering plants is placed under complex interactions between maternal tissues, the embryo, and the endosperm. The endosperm plays a major role in the regulation of seed size. In Arabidopsis thaliana, endosperm size depends on the coordination of the genetic pathway HAIKU (IKU) with epigene...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1305175110

    authors: Li J,Nie X,Tan JL,Berger F

    更新日期:2013-09-17 00:00:00

  • An 11-kDa form of human immunodeficiency virus protease expressed in Escherichia coli is sufficient for enzymatic activity.

    abstract::In order to define the protease domain of human immunodeficiency virus 1, various regions of the pol open reading frame were cloned and expressed in Escherichia coli. Antiserum directed against the conserved retroviral protease active site was used to identify pol precursor and processed species containing the presume...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.85.8.2449

    authors: Graves MC,Lim JJ,Heimer EP,Kramer RA

    更新日期:1988-04-01 00:00:00

  • Visual representations during saccadic eye movements.

    abstract::In normal vision, shifts of attention are usually followed by saccadic eye movements. Neurons in extrastriate area V4 are modulated by focal attention when eye movements are withheld, but they also respond in advance of visually guided saccadic eye movements. We have examined the visual selectivity of saccade-related ...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.95.15.8981

    authors: Moore T,Tolias AS,Schiller PH

    更新日期:1998-07-21 00:00:00