A precursor-inducible zebrafish model of acute protoporphyria with hepatic protein aggregation and multiorganelle stress

FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology
Jared S ElenbaasM Bishr Omary

Abstract

Protoporphyria is a metabolic disease that causes excess production of protoporphyrin IX (PP-IX), the final biosynthetic precursor to heme. Hepatic PP-IX accumulation may lead to end-stage liver disease. We tested the hypothesis that systemic administration of porphyrin precursors to zebrafish larvae results in protoporphyrin accumulation and a reproducible nongenetic porphyria model. Retro-orbital infusion of PP-IX or the iron chelator deferoxamine mesylate (DFO), with the first committed heme precursor α-aminolevulinic acid (ALA), generates high levels of PP-IX in zebrafish larvae. Exogenously infused or endogenously produced PP-IX accumulates preferentially in the liver of zebrafish larvae and peaks 1 to 3 d after infusion. Similar to patients with protoporphyria, PP-IX is excreted through the biliary system. Porphyrin accumulation in zebrafish liver causes multiorganelle protein aggregation as determined by mass spectrometry and immunoblotting. Endoplasmic reticulum stress and induction of autophagy were noted in zebrafish larvae and corroborated in 2 mouse models of protoporphyria. Furthermore, electron microscopy of zebrafish livers from larvae administered ALA + DFO showed hepatocyte autophagosomes, nuclear membrane ruff...Continue Reading

References

Sep 1, 1975·The Journal of Investigative Dermatology·F GschnaitK Wolff
Jan 1, 1992·Experimental and Clinical Endocrinology·G VassartR Paschke
Jan 1, 1992·Proceedings of the National Academy of Sciences of the United States of America·Y NakahashiS Sassa
Dec 1, 1990·Archives of Biochemistry and Biophysics·K M Morehouse, R P Mason
Dec 14, 1990·Biochemical and Biophysical Research Communications·Y NakahashiR Tokunaga
Sep 1, 1987·Archives of Biochemistry and Biophysics·K M MorehouseR P Mason
Feb 15, 1988·The Biochemical Journal·J Van SteveninckJ Van der Zee
Dec 1, 1973·Gut·R P ThompsonC H Gray
Apr 1, 1970·Die Naturwissenschaften·D Shemin
Jan 1, 1981·The British Journal of Dermatology·D M MacDonaldH Perrot
Apr 1, 1996·International Journal of Hematology·S Sassa, T Nagai
Jun 25, 1998·Photodermatology, Photoimmunology & Photomedicine·U GrossM O Doss
Nov 7, 1998·Nature Genetics·H WangS Lin
Sep 28, 1999·Free Radical Research·S AfonsoA Batlle
Dec 16, 2000·Journal of Inherited Metabolic Disease·U GrossM O Doss
Jan 12, 2002·The American Journal of Pathology·Kurt ZatloukalHelmut Denk
Jan 26, 2002·Medical Electron Microscopy : Official Journal of the Clinical Electron Microscopy Society of Japan·H KomatsuH Ishii
May 30, 2003·Biochemical Society Transactions·M R RedinboP M Potter
Jan 20, 2004·Trends in Cell Biology·D Thomas Rutkowski, Randal J Kaufman
Jan 20, 2004·Molecular and Cellular Biology·Hao-Yuan JiangRonald C Wek
Nov 13, 2004·The New England Journal of Medicine·M Bishr OmaryW H Irwin McLean
Jun 20, 2006·Current Opinion in Cell Biology·Lihong Zhao, Susan L Ackerman
Oct 4, 2006·Physiological Reviews·Stefan J Marciniak, David Ron
Apr 19, 2007·Nature Reviews. Genetics·Graham J Lieschke, Peter D Currie
Jun 15, 2007·Nature Reviews. Molecular Cell Biology·David Ron, Peter Walter
Aug 30, 2007·Journal of Environmental Pathology, Toxicology and Oncology : Official Organ of the International Society for Environmental Toxicology and Cancer·Alison Curnow, Andrew Pye
Jun 14, 2008·Experimental Hematology·Kimberly A DooleyUNKNOWN Tübingen 2000 Screen Consortium
Feb 10, 2009·Methods in Enzymology·Päivi Ylä-AnttilaEeva-Liisa Eskelinen
Sep 12, 2009·Orphanet Journal of Rare Diseases·Mario LechaJean-Charles Deybach
Sep 12, 2009·Nature Protocols·Charles K KaufmanLeonard Zon
Nov 6, 2009·Journal of the European Academy of Dermatology and Venereology : JEADV·J MaJ Wang
Dec 30, 2009·The Journal of Clinical Investigation·Kasper M A RouschopBradly G Wouters
Mar 2, 2010·Nature Reviews. Drug Discovery·Adriano Aguzzi, Tracy O'Connor
May 4, 2011·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Ayca CinarogluKirsten C Sadler
Feb 16, 2012·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Amika SinglaM Bishr Omary
Mar 1, 2012·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Raymond KwanM Bishr Omary

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Citations

Apr 1, 2017·American Journal of Physiology. Gastrointestinal and Liver Physiology·M Bishr Omary
Jun 25, 2019·Cellular and Molecular Gastroenterology and Hepatology·Dhiman MaitraM Bishr Omary
May 7, 2021·Scientific Reports·Juliana Bragazzi CunhaM Bishr Omary

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