Hemoglobinuria-related acute kidney injury is driven by intrarenal oxidative reactions triggering a heme toxicity response

Cell Death & Disease
J W DeuelDominik J Schaer

Abstract

Intravascular hemolysis can result in hemoglobinuria with acute kidney injury. In this study we systematically explored two in vivo animal models and a related cell culture system to identify hemoglobinuria-triggered damage pathways. In models of stored blood transfusion and hemoglobin (Hb) exposure in guinea pigs and beagle dogs we found that hemoglobinuria led to intrarenal conversion of ferrous Hb(Fe(2+)) to ferric Hb(Fe(3+)), accumulation of free heme and Hb-cross-linking products, enhanced 4-hydroxynonenal reactivity in renal tissue, and acute tubule injury. These changes were associated in guinea pigs with activation of a renal cortex gene expression signature indicative of oxidative stress and activation of the unfolded protein response (UPR). Tubule cells of hemolytic animals demonstrated enhanced protein expression of heme oxygenase and heat shock protein and enhanced expression of acute kidney injury-related neutrophil gelatinase-associated lipocalin. These adverse changes were completely prevented by haptoglobin treatment. The in vivo findings were extrapolated to a MS-based proteome analysis of SILAC-labeled renal epithelial cells that were exposed to free heme within a concentration range estimate of renal tubule h...Continue Reading

References

Nov 1, 1991·Arteriosclerosis and Thrombosis : a Journal of Vascular Biology·G BallaG M Vercellotti
Oct 15, 1993·Proceedings of the National Academy of Sciences of the United States of America·J BallaG M Vercellotti
Jul 20, 2002·Blood·Viktória JeneyGyörgy Balla
Nov 12, 2002·Nature Medicine·Christopher D ReiterMark T Gladwin
Mar 27, 2004·Nature Reviews. Drug Discovery·Abdu I Alayash
Jun 15, 2005·Annual Review of Biochemistry·Martin Schröder, Randal J Kaufman
Dec 21, 2006·The Journal of Biological Chemistry·Yiping JiaAbdu I Alayash
Jan 19, 2007·Journal of the American Society of Nephrology : JASN·Michal J TraczKarl A Nath
May 16, 2007·The Journal of Biological Chemistry·Rodrigo T FigueiredoMarcelo T Bozza
Apr 25, 2008·The New England Journal of Medicine·Martin Tombe
Dec 2, 2008·Nature Reviews. Drug Discovery·Inki KimJohn C Reed
Feb 26, 2010·Kidney International·Iris C Vermeulen WindsantMichael J Jacobs
Jul 8, 2010·American Journal of Kidney Diseases : the Official Journal of the National Kidney Foundation·Qi QianSanjeev Sethi
Jan 18, 2011·Nature Medicine·Neal ParagasJonathan Barasch
Jan 27, 2011·Methods in Enzymology·Christine M Oslowski, Fumihiko Urano
Feb 22, 2011·Free Radical Biology & Medicine·Frederic T BillingsMias Pretorius
Jul 21, 2011·Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association·José BallarínJuan Antonio Moreno
May 31, 2012·Journal of the American Chemical Society·Anna Maria SantoroDanilo Milardi
May 7, 2013·Cold Spring Harbor Perspectives in Medicine·Dominik J Schaer, Paul W Buehler
Sep 3, 2013·Cell Death and Differentiation·C A SchaerD J Schaer
Oct 3, 2013·The Journal of Clinical Investigation·Samit GhoshSolomon Fiifi Ofori-Acquah
Mar 4, 2014·Seminars in Cell & Developmental Biology·Lorenzo GalluzziAndreas Linkermann
Mar 7, 2014·Journal of the American Chemical Society·Rachid SkoutaBrent R Stockwell
Jun 4, 2014·Pediatric Nephrology : Journal of the International Pediatric Nephrology Association·Dima HamidehOfelia Alvarez
Sep 17, 2014·Proceedings of the National Academy of Sciences of the United States of America·Fabianno F DutraMarcelo T Bozza
Oct 11, 2014·Cell Death and Differentiation·F VallelianD J Schaer
Oct 18, 2014·Frontiers in Physiology·Viktória JeneyJózsef Balla
Nov 12, 2014·Proceedings of the National Academy of Sciences of the United States of America·Andreas LinkermannStefan Krautwald
Jul 15, 2015·Molecular Cell·Minghui GaoXuejun Jiang

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Citations

Sep 19, 2017·Pediatric Nephrology : Journal of the International Pediatric Nephrology Association·Emilie SaucierVasiliki Karava
Mar 21, 2017·American Journal of Physiology. Heart and Circulatory Physiology·Jan A GrawWarren M Zapol
May 12, 2018·Cell Death & Disease·Rachel P L van SwelmDorine W Swinkels
Jun 23, 2018·American Journal of Respiratory and Critical Care Medicine·Chong LeiWarren M Zapol
Jul 18, 2018·American Journal of Respiratory and Critical Care Medicine·Taijyu SatohMark T Gladwin
Jun 9, 2017·Journal of the American Society of Nephrology : JASN·Angel M SevillanoManuel Praga
Apr 28, 2018·BMC Veterinary Research·C Blasi BruguéRafael Ruiz de Gopegui
Oct 26, 2018·BMC Pharmacology & Toxicology·Hans Benno LeichtMonika Rau
Jan 9, 2020·The American Journal of Tropical Medicine and Hygiene·Kolitha H SellahewaKavindya Marapana
Oct 17, 2019·Experimental and Clinical Transplantation : Official Journal of the Middle East Society for Organ Transplantation·Saeyoung KimDaelim Jee
Apr 30, 2020·Biotechnology Progress·Ivan S Pires, Andre F Palmer
Aug 29, 2019·Nature Reviews. Nephrology·Kristof Van AvondtSacha Zeerleder
Jul 15, 2020·The Journal of Clinical Investigation·Marc PfefferléFlorence Vallelian
Aug 28, 2020·Frontiers in Immunology·Nicolas S MerleLubka T Roumenina
Mar 17, 2018·Frontiers in Immunology·Nicolas S MerleLubka T Roumenina
Aug 8, 2018·Toxicological Sciences : an Official Journal of the Society of Toxicology·Jin Hyen BaekPaul W Buehler
Jun 28, 2018·Intensive Care Medicine·Adrien PicodYves Cohen
Apr 16, 2019·ASAIO Journal : a Peer-reviewed Journal of the American Society for Artificial Internal Organs·Nicolas DufourMarie Thuong
Aug 10, 2019·Frontiers in Pharmacology·Bing WuWei Tang
Jan 8, 2020·Naunyn-Schmiedeberg's Archives of Pharmacology·Zuoyan WangJianjun Peng
Jul 25, 2019·Frontiers in Pharmacology·Alfonso Rubio-NavarroJuan Antonio Moreno
Jan 17, 2021·The Journal of Thoracic and Cardiovascular Surgery·Betty PatUNKNOWN Clinical Working Group
May 24, 2020·Kidney International·Yogesh ScindiaSundararaman Swaminathan
Mar 19, 2020·Biomacromolecules·Ivan S PiresAndre F Palmer
Jun 27, 2020·Trends in Molecular Medicine·Paul W BuehlerDominik J Schaer
Jun 7, 2020·Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences·Brandon TimmJacob Elmer
Feb 28, 2019·Néphrologie & thérapeutique·Julie ZettlBenjamin Savenkoff
Aug 8, 2021·Microorganisms·Claire Roger, Benjamin Louart
Mar 21, 2019·Toxicon : Official Journal of the International Society on Toxinology·Rana DizajiMir-Jamal Hosseini

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