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Ferroptosis contributes to hemolytic hyperbilirubinemia‑induced brain damage in vivo and in vitro
Ferroptosis is driven by iron-dependent accumulation of lipid hydroperoxides, and hemolytic hyperbilirubinemia causes accumulation of unconjugated bilirubin and iron. The present study aimed to assess the role of ferroptosis in hemolytic hyperbilirubinemia-induced brain damage (HHIBD). Rats were ran...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
D.A. Spandidos
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10668077/ https://www.ncbi.nlm.nih.gov/pubmed/37937619 http://dx.doi.org/10.3892/mmr.2023.13123 |
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author | Zhou, Jinfu Lin, Xinpei Liao, Sining Li, Guilin Tang, Jianping Luo, Jinying Zhang, Chenran Wu, Siying Xu, Liangpu Li, Huangyuan |
author_facet | Zhou, Jinfu Lin, Xinpei Liao, Sining Li, Guilin Tang, Jianping Luo, Jinying Zhang, Chenran Wu, Siying Xu, Liangpu Li, Huangyuan |
author_sort | Zhou, Jinfu |
collection | PubMed |
description | Ferroptosis is driven by iron-dependent accumulation of lipid hydroperoxides, and hemolytic hyperbilirubinemia causes accumulation of unconjugated bilirubin and iron. The present study aimed to assess the role of ferroptosis in hemolytic hyperbilirubinemia-induced brain damage (HHIBD). Rats were randomly divided into the control, phenylhydrazine (PHZ) and deferoxamine (DFO) + PHZ groups, with 12 rats in each group. Ferroptosis-associated biochemical and protein indicators were measured in the brain tissue of rats. We also performed tandem mass tag-labeled proteomic analysis. The levels of iron and malondialdehyde were significantly higher and levels of glutathione (GSH) and superoxide dismutase activity significantly lower in the brain tissues of the PHZ group compared with those in the control group. HHIBD also resulted in significant increases in the expression of the ferroptosis-related proteins acyl-CoA synthetase long-chain family member 4, ferritin heavy chain 1 and transferrin receptor and divalent metal transporter 1, as well as a significant reduction in the expression of ferroptosis suppressor protein 1. Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis demonstrated that the differentially expressed proteins of rat brain tissues between the control and PHZ groups were significantly involved in ferroptosis, GSH metabolism and fatty acid biosynthesis pathways. Pretreatment with DFO induced antioxidant activity and alleviated lipid peroxidation-mediated HHIBD. In addition, PC12 cells treated with ferric ammonium citrate showed shrinking mitochondria, high mitochondrial membrane density, and increased lipid reactive oxygen species and intracellular ferrous iron, which were antagonized by pretreatment with ferrostatin-1 or DFO, which was reversed by pretreatment with ferrostatin-1 or DFO. The present study demonstrated that ferroptosis is involved in HHIBD and provided novel insights into candidate proteins that are potentially involved in ferroptosis in the brain during hemolytic hyperbilirubinemia. |
format | Online Article Text |
id | pubmed-10668077 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | D.A. Spandidos |
record_format | MEDLINE/PubMed |
spelling | pubmed-106680772023-11-03 Ferroptosis contributes to hemolytic hyperbilirubinemia‑induced brain damage in vivo and in vitro Zhou, Jinfu Lin, Xinpei Liao, Sining Li, Guilin Tang, Jianping Luo, Jinying Zhang, Chenran Wu, Siying Xu, Liangpu Li, Huangyuan Mol Med Rep Articles Ferroptosis is driven by iron-dependent accumulation of lipid hydroperoxides, and hemolytic hyperbilirubinemia causes accumulation of unconjugated bilirubin and iron. The present study aimed to assess the role of ferroptosis in hemolytic hyperbilirubinemia-induced brain damage (HHIBD). Rats were randomly divided into the control, phenylhydrazine (PHZ) and deferoxamine (DFO) + PHZ groups, with 12 rats in each group. Ferroptosis-associated biochemical and protein indicators were measured in the brain tissue of rats. We also performed tandem mass tag-labeled proteomic analysis. The levels of iron and malondialdehyde were significantly higher and levels of glutathione (GSH) and superoxide dismutase activity significantly lower in the brain tissues of the PHZ group compared with those in the control group. HHIBD also resulted in significant increases in the expression of the ferroptosis-related proteins acyl-CoA synthetase long-chain family member 4, ferritin heavy chain 1 and transferrin receptor and divalent metal transporter 1, as well as a significant reduction in the expression of ferroptosis suppressor protein 1. Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis demonstrated that the differentially expressed proteins of rat brain tissues between the control and PHZ groups were significantly involved in ferroptosis, GSH metabolism and fatty acid biosynthesis pathways. Pretreatment with DFO induced antioxidant activity and alleviated lipid peroxidation-mediated HHIBD. In addition, PC12 cells treated with ferric ammonium citrate showed shrinking mitochondria, high mitochondrial membrane density, and increased lipid reactive oxygen species and intracellular ferrous iron, which were antagonized by pretreatment with ferrostatin-1 or DFO, which was reversed by pretreatment with ferrostatin-1 or DFO. The present study demonstrated that ferroptosis is involved in HHIBD and provided novel insights into candidate proteins that are potentially involved in ferroptosis in the brain during hemolytic hyperbilirubinemia. D.A. Spandidos 2023-11-03 /pmc/articles/PMC10668077/ /pubmed/37937619 http://dx.doi.org/10.3892/mmr.2023.13123 Text en Copyright: © Zhou et al. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License (https://creativecommons.org/licenses/by-nc-nd/4.0/) , which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made. |
spellingShingle | Articles Zhou, Jinfu Lin, Xinpei Liao, Sining Li, Guilin Tang, Jianping Luo, Jinying Zhang, Chenran Wu, Siying Xu, Liangpu Li, Huangyuan Ferroptosis contributes to hemolytic hyperbilirubinemia‑induced brain damage in vivo and in vitro |
title | Ferroptosis contributes to hemolytic hyperbilirubinemia‑induced brain damage in vivo and in vitro |
title_full | Ferroptosis contributes to hemolytic hyperbilirubinemia‑induced brain damage in vivo and in vitro |
title_fullStr | Ferroptosis contributes to hemolytic hyperbilirubinemia‑induced brain damage in vivo and in vitro |
title_full_unstemmed | Ferroptosis contributes to hemolytic hyperbilirubinemia‑induced brain damage in vivo and in vitro |
title_short | Ferroptosis contributes to hemolytic hyperbilirubinemia‑induced brain damage in vivo and in vitro |
title_sort | ferroptosis contributes to hemolytic hyperbilirubinemia‑induced brain damage in vivo and in vitro |
topic | Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10668077/ https://www.ncbi.nlm.nih.gov/pubmed/37937619 http://dx.doi.org/10.3892/mmr.2023.13123 |
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