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Exacerbation of Neonatal Hemolysis and Impaired Renal Iron Handling in Heme Oxygenase 1-Deficient Mice

In most mammals, neonatal intravascular hemolysis is a benign and moderate disorder that usually does not lead to anemia. During the neonatal period, kidneys play a key role in detoxification and recirculation of iron species released from red blood cells (RBC) and filtered out by glomeruli to the p...

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Autores principales: Bednarz, Aleksandra, Lipiński, Paweł, Starzyński, Rafał R., Tomczyk, Mateusz, Kraszewska, Izabela, Herman, Sylwia, Kowalski, Kacper, Gruca, Ewelina, Jończy, Aneta, Mazgaj, Rafał, Szudzik, Mateusz, Rajfur, Zenon, Baster, Zbigniew, Józkowicz, Alicja, Lenartowicz, Małgorzata
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7589678/
https://www.ncbi.nlm.nih.gov/pubmed/33092142
http://dx.doi.org/10.3390/ijms21207754
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author Bednarz, Aleksandra
Lipiński, Paweł
Starzyński, Rafał R.
Tomczyk, Mateusz
Kraszewska, Izabela
Herman, Sylwia
Kowalski, Kacper
Gruca, Ewelina
Jończy, Aneta
Mazgaj, Rafał
Szudzik, Mateusz
Rajfur, Zenon
Baster, Zbigniew
Józkowicz, Alicja
Lenartowicz, Małgorzata
author_facet Bednarz, Aleksandra
Lipiński, Paweł
Starzyński, Rafał R.
Tomczyk, Mateusz
Kraszewska, Izabela
Herman, Sylwia
Kowalski, Kacper
Gruca, Ewelina
Jończy, Aneta
Mazgaj, Rafał
Szudzik, Mateusz
Rajfur, Zenon
Baster, Zbigniew
Józkowicz, Alicja
Lenartowicz, Małgorzata
author_sort Bednarz, Aleksandra
collection PubMed
description In most mammals, neonatal intravascular hemolysis is a benign and moderate disorder that usually does not lead to anemia. During the neonatal period, kidneys play a key role in detoxification and recirculation of iron species released from red blood cells (RBC) and filtered out by glomeruli to the primary urine. Activity of heme oxygenase 1 (HO1), a heme-degrading enzyme localized in epithelial cells of proximal tubules, seems to be of critical importance for both processes. We show that, in HO1 knockout mouse newborns, hemolysis was prolonged despite a transient state and exacerbated, which led to temporal deterioration of RBC status. In neonates lacking HO1, functioning of renal molecular machinery responsible for iron reabsorption from the primary urine (megalin/cubilin complex) and its transfer to the blood (ferroportin) was either shifted in time or impaired, respectively. Those abnormalities resulted in iron loss from the body (excreted in urine) and in iron retention in the renal epithelium. We postulate that, as a consequence of these abnormalities, a tight systemic iron balance of HO1 knockout neonates may be temporarily affected.
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spelling pubmed-75896782020-10-29 Exacerbation of Neonatal Hemolysis and Impaired Renal Iron Handling in Heme Oxygenase 1-Deficient Mice Bednarz, Aleksandra Lipiński, Paweł Starzyński, Rafał R. Tomczyk, Mateusz Kraszewska, Izabela Herman, Sylwia Kowalski, Kacper Gruca, Ewelina Jończy, Aneta Mazgaj, Rafał Szudzik, Mateusz Rajfur, Zenon Baster, Zbigniew Józkowicz, Alicja Lenartowicz, Małgorzata Int J Mol Sci Article In most mammals, neonatal intravascular hemolysis is a benign and moderate disorder that usually does not lead to anemia. During the neonatal period, kidneys play a key role in detoxification and recirculation of iron species released from red blood cells (RBC) and filtered out by glomeruli to the primary urine. Activity of heme oxygenase 1 (HO1), a heme-degrading enzyme localized in epithelial cells of proximal tubules, seems to be of critical importance for both processes. We show that, in HO1 knockout mouse newborns, hemolysis was prolonged despite a transient state and exacerbated, which led to temporal deterioration of RBC status. In neonates lacking HO1, functioning of renal molecular machinery responsible for iron reabsorption from the primary urine (megalin/cubilin complex) and its transfer to the blood (ferroportin) was either shifted in time or impaired, respectively. Those abnormalities resulted in iron loss from the body (excreted in urine) and in iron retention in the renal epithelium. We postulate that, as a consequence of these abnormalities, a tight systemic iron balance of HO1 knockout neonates may be temporarily affected. MDPI 2020-10-20 /pmc/articles/PMC7589678/ /pubmed/33092142 http://dx.doi.org/10.3390/ijms21207754 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Bednarz, Aleksandra
Lipiński, Paweł
Starzyński, Rafał R.
Tomczyk, Mateusz
Kraszewska, Izabela
Herman, Sylwia
Kowalski, Kacper
Gruca, Ewelina
Jończy, Aneta
Mazgaj, Rafał
Szudzik, Mateusz
Rajfur, Zenon
Baster, Zbigniew
Józkowicz, Alicja
Lenartowicz, Małgorzata
Exacerbation of Neonatal Hemolysis and Impaired Renal Iron Handling in Heme Oxygenase 1-Deficient Mice
title Exacerbation of Neonatal Hemolysis and Impaired Renal Iron Handling in Heme Oxygenase 1-Deficient Mice
title_full Exacerbation of Neonatal Hemolysis and Impaired Renal Iron Handling in Heme Oxygenase 1-Deficient Mice
title_fullStr Exacerbation of Neonatal Hemolysis and Impaired Renal Iron Handling in Heme Oxygenase 1-Deficient Mice
title_full_unstemmed Exacerbation of Neonatal Hemolysis and Impaired Renal Iron Handling in Heme Oxygenase 1-Deficient Mice
title_short Exacerbation of Neonatal Hemolysis and Impaired Renal Iron Handling in Heme Oxygenase 1-Deficient Mice
title_sort exacerbation of neonatal hemolysis and impaired renal iron handling in heme oxygenase 1-deficient mice
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7589678/
https://www.ncbi.nlm.nih.gov/pubmed/33092142
http://dx.doi.org/10.3390/ijms21207754
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