PMID: 9422375Jan 9, 1998Paper

3-Hydroxykynurenine, an endogenous oxidative stress generator, causes neuronal cell death with apoptotic features and region selectivity

Journal of Neurochemistry
S OkudaH Katsuki

Abstract

3-Hydroxykynurenine (3-HK) is a potential endogenous neurotoxin whose increased levels have been described in several neurodegenerative disorders. Here, we characterized in vitro neurotoxicity of 3-HK. Of the tested kynurenine pathway metabolites, only 3-HK, and to a lesser extent 3-hydroxyanthranilic acid, were toxic to primary cultured striatal neurons. 3-HK toxicity was inhibited by various antioxidants, indicating that the generation of reactive oxygen species is essential to the toxicity. 3-HK-induced neuronal cell death showed several features of apoptosis, as determined by the blockade by macromolecule synthesis inhibitors, and by the observation of cell body shrinkage with nuclear chromatin condensation and fragmentation. In addition, 3-HK toxicity was dependent on its cellular uptake via transporters for large neutral amino acids, because uptake inhibition blocked the toxicity. Cortical and striatal neurons were much more vulnerable to 3-HK toxicity than cerebellar neurons, which may be attributable to the differences in transporter activities of these neurons. These results indicate that 3-HK, depending on transporter-mediated cellular uptake and on intracellular generation of oxidative stress, induces neuronal cell d...Continue Reading

Citations

Sep 18, 2002·The Journal of Pharmacology and Experimental Therapeutics·Robert Schwarcz, Roberto Pellicciari
Oct 31, 2002·Nature Reviews. Drug Discovery·Trevor W Stone, L Gail Darlington
Aug 28, 2003·Clinical Chemistry and Laboratory Medicine : CCLM·Trevor W StoneL Gail Darlington
Oct 27, 2004·Journal of Inherited Metabolic Disease·S Varadkar, R Surtees
Apr 20, 2005·Journal of Neurochemistry·N StoyL G Darlington
Oct 11, 2005·International Journal of Developmental Neuroscience : the Official Journal of the International Society for Developmental Neuroscience·Guilhian LeipnitzAlexandra Latini
Jan 20, 2006·European Journal of Neurology : the Official Journal of the European Federation of Neurological Societies·G M MackayL G Darlington
May 10, 2006·The Biochemical Journal·Qian HanJianyong Li
Dec 14, 2007·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·Jonathan P GodboutRodney W Johnson
Jun 6, 2009·Blood Coagulation & Fibrinolysis : an International Journal in Haemostasis and Thrombosis·Krystyna PawlakDariusz Pawlak
Mar 25, 2009·Laboratory Investigation; a Journal of Technical Methods and Pathology·Maneesh MailankotRam H Nagaraj
Oct 26, 2010·Amino Acids·Lukasz R KolodziejRichard O Williams
Jul 26, 2011·Journal of Neural Transmission·Vilma GabbayLeonard Liebes
Aug 23, 2011·Journal of Neural Transmission·Dénes ZádoriLászló Vécsei
Jun 22, 2013·Journal of Neurochemistry·Gelareh MazareiBlair R Leavitt
May 3, 2013·Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte·Marta AmaralFlaviano Giorgini
Mar 19, 2014·PloS One·Malihe-Sadat Poormasjedi-MeibodAziz Ghahary
Sep 3, 2014·Journal of Neuroinflammation·David J Allison, David S Ditor
Aug 20, 2016·Frontiers in Immunology·Michael D LovelaceBruce J Brew
Nov 20, 2016·PLoS Computational Biology·Aleksandr V ZhuravlevElena V Savvateeva-Popova
May 31, 2018·International Journal of Tryptophan Research : IJTR·Rosemary A FrickerSíle M Griffin
Sep 19, 2018·Expert Opinion on Therapeutic Targets·Radhika SharmaAnurag Kuhad
Dec 12, 2018·PLoS Computational Biology·Aleksandr V ZhuravlevElena V Savvateeva-Popova
Mar 16, 2019·Frontiers in Molecular Biosciences·Franca RossiMenico Rizzi
Jan 5, 2000·Journal of Neurochemistry·P S Sastry, K S Rao
Feb 4, 1999·Journal of Neurochemistry·P S HodgkinsR Schwarcz
Jan 18, 2005·Biological Chemistry·Christiana WinklerDietmar Fuchs
Dec 8, 2006·Cellular and Molecular Neurobiology·Patrícia Fernanda SchuckMoacir Wajner
Aug 9, 2011·Journal of Neurochemistry·Caroline M ForrestTrevor W Stone
May 20, 2010·Journal of Pediatric Endocrinology & Metabolism : JPEM·J UberosA Muñoz-Hoyos
Jul 28, 2012·International Journal of Tryptophan Research : IJTR·Diba SheipouriGilles J Guillemin
Dec 6, 2011·Journal of Neural Transmission·Aye-Mu MyintNorbert Müller
Aug 31, 2013·Journal of Molecular Neuroscience : MN·Heidi OrmstadLeiv Sandvik
Jul 19, 2016·The World Journal of Biological Psychiatry : the Official Journal of the World Federation of Societies of Biological Psychiatry·Chutima RoomruangwongMichael Maes
Apr 27, 2016·Proceedings of the National Academy of Sciences of the United States of America·Carlo BredaFlaviano Giorgini

❮ Previous
Next ❯

Related Concepts

Related Feeds

Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis