Abstract
Phytanic acid, a saturated fatty acid of 20-carbon-atoms with isoprenoic structure, is formed from the phytol-side chain of chlorophyll in ruminants. Degradation of phytanic acid is blocked in Refsum disease by several enzymatic defects of peroxisomal degradation of branched-chain fatty acids. Refsum disease is an inherited neurological disorder progressively developing from early childhood to adultness. Clinical signs are attributed to toxicity of phytanic acid, which accumulates to unusually high levels in the tissue and serum of patients suffering from untreated Refsum disease. We report here that hippocampal astrocytes isolated from rat brain, which were exposed to phytanic acid (50 microM) die within a few hours. In situ depolarization of mitochondria and an increase of cytosolic Ca2+ precede cell death. Therefore, we also investigated the influence of phytanic acid on physiology of mitochondria isolated from rat brain. Mitochondria become functionally impaired by phytanic acid, as indicated by uncoupling (resting state), inhibition of the electron transport (state 3), stimulation of ROS-generation, decline of Ca2+ loading and severe release of cytochrome c. Thus, phytanic acid seems to initiate astrocyte cell death by act...Continue Reading
References
Oct 1, 1976·FEBS Letters·K E Akerman, M K Wikström
Oct 1, 1990·Journal of Bioenergetics and Biomembranes·S LuvisettoG F Azzone
Mar 14, 1995·Biochimica Et Biophysica Acta·Y ShinoharaH Terada
Dec 9, 1997·Cell·P LiX Wang
Sep 3, 1999·FEBS Letters·P Schönfeld, H Struy
Aug 10, 2000·Journal of Neuroscience Research·S Kahlert, G Reiser
Feb 24, 2001·International Ophthalmology Clinics·C A Grant, E L Berson
Jan 10, 2002·The Journal of Biological Chemistry·Esa K J TuominenPaavo K J Kinnunen
Apr 12, 2002·Journal of Neurochemistry·Yuanbin LiuDavid Schubert
Jun 11, 2002·Methods : a Companion to Methods in Enzymology·Mauro Degli Esposti
Oct 9, 2002·The Journal of Biological Chemistry·Susanne IdelUdo Seedorf
Mar 14, 2003·Biochimica Et Biophysica Acta·Ronald J A WandersMatthew D Lloyd
Jun 17, 2004·The Biochemical Journal·Peter SchönfeldGeorg Reiser
Jul 13, 2004·Brain Research. Developmental Brain Research·Courtney L RobertsonGary Fiskum
Aug 12, 2004·Free Radical Biology & Medicine·Martin D BrandNadeene Parker
Jan 15, 2005·Neurobiology of Disease·Stefan KahlertGeorg Reiser
Apr 30, 2005·Trends in Pharmacological Sciences·Joel P BergerPeter T Meinke
Sep 24, 2005·Annals of Neurology·M Flint Beal
Jan 3, 2006·International Journal of Developmental Neuroscience : the Official Journal of the International Society for Developmental Neuroscience·Georg ReiserStefan Kahlert
Citations
Nov 14, 2008·Proceedings of the National Academy of Sciences of the United States of America·Sacha FerdinandussePedro Brites
Jun 19, 2010·Journal of Lipid Research·Paul P Van Veldhoven
Feb 5, 2013·Progress in Lipid Research·Matthew D LloydTimothy J Woodman
May 17, 2011·Neurobiology of Disease·Nicol Kruska, Georg Reiser
Jul 19, 2015·Neuroscience·C G BorgesM Wajner
Oct 2, 2007·Journal of the Neurological Sciences·Josef FinstererTill Voigtländer
Apr 27, 2016·Aging and Disease·Peter Schönfeld, Georg Reiser
Jun 16, 2015·Frontiers in Cell and Developmental Biology·Celien LismontMarc Fransen
Oct 28, 2016·Molecular Neurobiology·Shaista ChaudharySuhel Parvez
May 31, 2018·Neuromolecular Medicine·María Belén Ruiz-RosoBeatriz Martín-Fernández
Aug 23, 2019·European Journal of Cancer Prevention : the Official Journal of the European Cancer Prevention Organisation (ECP)·Gerd BobeYumie Takata