Antiretroviral nucleosides, deoxynucleotide carrier and mitochondrial DNA: evidence supporting the DNA pol gamma hypothesis

AIDS
William LewisRobert Santoianni

Abstract

Nucleoside reverse transcriptase inhibitors (NRTIs) exhibit mitochondrial toxicity. The mitochondrial deoxynucleotide carrier (DNC) transports nucleotide precursors (or phosphorylated NRTIs) into mitochondria for mitochondrial (mt)DNA replication or inhibition of mtDNA replication by NRTIs. Transgenic mice (TG) expressing human DNC targeted to murine myocardium served to define mitochondrial events from NRTIs in vivo and findings were corroborated by biochemical events in vitro. Zidovudine (3'-azido-2',3'-deoxythymidine; ZDV), stavudine (2', 3'-didehydro-2', 3'-deoxythymidine; d4T), or lamivudine ((-)-2'-deoxy-3'-thiacytidine; 3TC) were administered individually to TGs and wild-type (WT) littermates (35 days) at human doses with drug-free vehicle as control. Left ventricle (LV) mass was defined echocardiographically, mitochondrial ultrastructural defects were identified by electron microscopy, the abundance of cardiac mtDNA was quantified by real time polymerase chain reaction, and mtDNA-encoded polypeptides were quantified. Untreated TGs exhibited normal LV mass with minor mitochondrial damage. NRTI monotherapy (either d4T or ZDV) increased LV mass in TGs and caused significant mitochondrial destruction. Cardiac mtDNA was depl...Continue Reading

References

Apr 19, 1990·The New England Journal of Medicine·M C DalakasJ L Griffin
Feb 7, 1989·Biochemistry·T A Kunkel, D W Mosbaugh
Oct 26, 1995·The New England Journal of Medicine·M N Swartz
May 1, 1995·Nature Medicine·W Lewis, M C Dalakas
Aug 11, 1995·The Journal of Biological Chemistry·S ErikssonD A Clayton
Jun 6, 1994·FEBS Letters·F Palmieri
Jul 10, 1998·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·B C TennantJ L Gerin
Mar 4, 2000·Laboratory Investigation; a Journal of Technical Methods and Pathology·W LewisP Klotman
Jun 9, 2000·Annual Review of Physiology·J Robbins
Feb 28, 2001·Proceedings of the National Academy of Sciences of the United States of America·V DolceJ E Walker
Apr 25, 2001·The Journal of Biological Chemistry·S E Lim, W C Copeland
May 1, 2001·The Journal of Biological Chemistry·J Y FengK S Anderson
Jun 15, 2001·Laboratory Investigation; a Journal of Technical Methods and Pathology·W LewisB J Day
Aug 30, 2001·The Journal of Biological Chemistry·A A JohnsonK A Johnson
Nov 14, 2001·Laboratory Investigation; a Journal of Technical Methods and Pathology·W LewisA M Samarel
Dec 18, 2001·BioEssays : News and Reviews in Molecular, Cellular and Developmental Biology·A CossarizzaA Viganò
Apr 18, 2002·American Journal of Physiology. Heart and Circulatory Physiology·Scott M RaidelWilliam Lewis
Aug 20, 2002·Nature Genetics·Marjorie J RosenbergLeslie G Biesecker
Mar 26, 2003·Human Mutation·R CarrozzoJ Arenas
May 9, 2003·Pediatric Research·Orly Elpeleg
Oct 4, 2003·Nature Reviews. Drug Discovery·William LewisWilliam C Copeland
Nov 5, 2003·Pflügers Archiv : European journal of physiology·Ferdinando Palmieri
Nov 20, 2003·Critical Care : the Official Journal of the Critical Care Forum·Ehsan Y DavaniDelbert R Dorscheid
Jun 11, 2004·Annual Review of Biochemistry·Laurie S Kaguni
Jul 20, 2004·Nature Structural & Molecular Biology·Maria A GraziewiczWilliam C Copeland
Aug 4, 2004·Toxicology and Applied Pharmacology·Leonard W VelsorBrian J Day

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Citations

Jul 10, 2007·Cell Biology and Toxicology·H LiuZ Li
Feb 5, 2009·Current Diabetes Reports·Giuseppe Barbaro, Gialuca Iacobellis
Apr 10, 2010·Cardiovascular Toxicology·James J KohlerWilliam Lewis
Apr 9, 2008·Chemical Research in Toxicology·James J KohlerWilliam Lewis
Oct 18, 2007·Nucleic Acids Research·Jeremiah W Hanes, Kenneth A Johnson
Sep 1, 2012·The Pediatric Infectious Disease Journal·Brian KirmseWilliam Borkowsky
Nov 14, 2008·AIDS·Sher L HendricksonStephen J O'Brien
Apr 3, 2009·Journal of Acquired Immune Deficiency Syndromes : JAIDS·Sher L HendricksonStephen J O'Brien
Feb 8, 2007·American Journal of Physiology. Endocrinology and Metabolism·Amy FleischmanSteven K Grinspoon
Aug 25, 2009·PLoS Computational Biology·James Corey AdamsPatricia C Babbitt
Feb 20, 2010·Therapeutics and Clinical Risk Management·Iwen F GrigsbyKim C Mansky
Jul 20, 2012·Journal of Neurovirology·Kevin RobertsonRick B Meeker
Sep 10, 2010·Journal of Acquired Immune Deficiency Syndromes : JAIDS·Kerstin BalcarekUlrich A Walker
Jul 1, 2007·Current Opinion in HIV and AIDS·Hélène C F Côté
Aug 27, 2013·Expert Review of Cardiovascular Therapy·Rami Alharethi
Mar 29, 2008·Expert Opinion on Drug Metabolism & Toxicology·Brian Eley
Oct 6, 2007·Expert Opinion on Drug Metabolism & Toxicology·George P H Leung, Chung-Ming Tse
Mar 8, 2008·Expert Opinion on Drug Safety·Vilma A SardãoPaulo J Oliveira
Apr 19, 2012·Expert Opinion on Drug Metabolism & Toxicology·Christopher A KoczorWilliam Lewis
Nov 17, 2010·Clinics in Perinatology·Andres F Camacho-GonzalezRana Chakraborty
Jan 1, 2008·Bioorganic & Medicinal Chemistry Letters·Constantine G BoojamraTomas Cihlar
Sep 25, 2007·Journal of Clinical Densitometry : the Official Journal of the International Society for Clinical Densitometry·C DelpierreJ Bernard
Sep 8, 2010·Developmental Disabilities Research Reviews·Bruce H Cohen
May 24, 2006·Antiviral Research·Raymond F SchinaziSelwyn J Hurwitz
Nov 20, 2009·Scandinavian Journal of Infectious Diseases·Anne Maagaard, Dag Kvale
Aug 4, 2012·Bioorganic & Medicinal Chemistry Letters·Hitesh K AgarwalKeykavous Parang
Feb 21, 2007·Laboratory Investigation; a Journal of Technical Methods and Pathology·William LewisWilliam C Copeland
Oct 24, 2012·Laboratory Investigation; a Journal of Technical Methods and Pathology·Christopher A KoczorWilliam Lewis
Jan 13, 2010·Laboratory Investigation; a Journal of Technical Methods and Pathology·James J KohlerWilliam Lewis

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