Embryonal erythropoiesis and aging exploit ferroptosis
Ferroptosis is a form of regulated cell necrosis, as a consequence of Fe(II)-dependent lipid peroxidation. Although ferroptosis has been linked to cancer cell death, neurodegeneration and reperfusion injury, physiological roles of ferroptosis have not been elucidated to date mostly due to the lack o...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2021-12-01
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| Series: | Redox Biology |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2213231721003359 |
| _version_ | 1819174539120082944 |
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| author | Hao Zheng Li Jiang Tsuyoshi Tsuduki Marcus Conrad Shinya Toyokuni |
| author_facet | Hao Zheng Li Jiang Tsuyoshi Tsuduki Marcus Conrad Shinya Toyokuni |
| author_sort | Hao Zheng |
| collection | DOAJ |
| description | Ferroptosis is a form of regulated cell necrosis, as a consequence of Fe(II)-dependent lipid peroxidation. Although ferroptosis has been linked to cancer cell death, neurodegeneration and reperfusion injury, physiological roles of ferroptosis have not been elucidated to date mostly due to the lack of appropriate methodologies. Here, we show that 4-hydroxy-2-nonenal (HNE)-modified proteins detected by a HNEJ-1 mouse monoclonal antibody is a robust immunohistochemical technology to locate ferroptosis in tissues in combination with morphological nuclear information, based on various models of ferroptosis, including erastin-induced cysteine-deprivation, conditional Gpx4 knockout and Fe(II)-dependent renal tubular injury, as well as other types of regulated cell death. Specificity of HNEJ-1 with ferroptosis was endorsed by non-selective identification of HNE-modified proteins in an Fe(II)-dependent renal tubular injury model. We further comprehensively searched for signs of ferroptosis in different developmental stages of Fischer-344 rats from E9.5–2.5 years of age. We observed that there was a significant age-dependent increase in ferroptosis in the kidney, spleen, liver, ovary, uterus, cerebellum and bone marrow, which was accompanied by iron accumulation. Not only phagocytic cells but also parenchymal cells were affected. Epidermal ferroptosis in ageing SAMP8 mice was significantly promoted by high-fat or carbohydrate-restricted diets. During embryogenesis of Fischer-344 rats, we found ferroptosis in nucleated erythrocytes at E13.5, which disappeared in enucleated erythrocytes at E18.5. Administration of a ferroptosis inhibitor, liproxstatin-1, significantly delayed erythrocyte enucleation. Therefore, our results demonstrate for the first time the involvement of ferroptosis in physiological processes, such as embryonic erythropoiesis and aging, suggesting the evolutionally acquired mechanism and the inevitable side effects, respectively. |
| first_indexed | 2024-12-22T20:40:34Z |
| format | Article |
| id | doaj.art-131bfd2830cb4dbfbfbbca2745536a99 |
| institution | Directory Open Access Journal |
| issn | 2213-2317 |
| language | English |
| last_indexed | 2024-12-22T20:40:34Z |
| publishDate | 2021-12-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Redox Biology |
| spelling | doaj.art-131bfd2830cb4dbfbfbbca2745536a992022-12-21T18:13:20ZengElsevierRedox Biology2213-23172021-12-0148102175Embryonal erythropoiesis and aging exploit ferroptosisHao Zheng0Li Jiang1Tsuyoshi Tsuduki2Marcus Conrad3Shinya Toyokuni4Department of Pathology and Biological Responses, Nagoya University Graduate School of Medicine, Nagoya, 466-8550, JapanDepartment of Pathology and Biological Responses, Nagoya University Graduate School of Medicine, Nagoya, 466-8550, JapanLaboratory of Food and Biomolecular Science, Graduate School of Agriculture, Tohoku University, 468-1, Aoba, Aramaki, Aoba-ku, Sendai, 980-0845, JapanHelmholtz Zentrum München, Institute of Metabolism and Cell Death, 85764, Neuherberg, Germany; Pirogov National Research Medical University, Laboratory of Experimental Oncology, Ostrovityanova 1, Moscow, 117997, RussiaDepartment of Pathology and Biological Responses, Nagoya University Graduate School of Medicine, Nagoya, 466-8550, Japan; Center for Low-temperature Plasma Sciences, Nagoya University, Furo-cho, Chikusa, Nagoya, 464-8603, Japan; Corresponding author. Department of Pathology and Biological Responses, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, Japan.Ferroptosis is a form of regulated cell necrosis, as a consequence of Fe(II)-dependent lipid peroxidation. Although ferroptosis has been linked to cancer cell death, neurodegeneration and reperfusion injury, physiological roles of ferroptosis have not been elucidated to date mostly due to the lack of appropriate methodologies. Here, we show that 4-hydroxy-2-nonenal (HNE)-modified proteins detected by a HNEJ-1 mouse monoclonal antibody is a robust immunohistochemical technology to locate ferroptosis in tissues in combination with morphological nuclear information, based on various models of ferroptosis, including erastin-induced cysteine-deprivation, conditional Gpx4 knockout and Fe(II)-dependent renal tubular injury, as well as other types of regulated cell death. Specificity of HNEJ-1 with ferroptosis was endorsed by non-selective identification of HNE-modified proteins in an Fe(II)-dependent renal tubular injury model. We further comprehensively searched for signs of ferroptosis in different developmental stages of Fischer-344 rats from E9.5–2.5 years of age. We observed that there was a significant age-dependent increase in ferroptosis in the kidney, spleen, liver, ovary, uterus, cerebellum and bone marrow, which was accompanied by iron accumulation. Not only phagocytic cells but also parenchymal cells were affected. Epidermal ferroptosis in ageing SAMP8 mice was significantly promoted by high-fat or carbohydrate-restricted diets. During embryogenesis of Fischer-344 rats, we found ferroptosis in nucleated erythrocytes at E13.5, which disappeared in enucleated erythrocytes at E18.5. Administration of a ferroptosis inhibitor, liproxstatin-1, significantly delayed erythrocyte enucleation. Therefore, our results demonstrate for the first time the involvement of ferroptosis in physiological processes, such as embryonic erythropoiesis and aging, suggesting the evolutionally acquired mechanism and the inevitable side effects, respectively.http://www.sciencedirect.com/science/article/pii/S2213231721003359FerroptosisIron4-Hydroxy-2-nonenalErythropoiesisAging |
| spellingShingle | Hao Zheng Li Jiang Tsuyoshi Tsuduki Marcus Conrad Shinya Toyokuni Embryonal erythropoiesis and aging exploit ferroptosis Redox Biology Ferroptosis Iron 4-Hydroxy-2-nonenal Erythropoiesis Aging |
| title | Embryonal erythropoiesis and aging exploit ferroptosis |
| title_full | Embryonal erythropoiesis and aging exploit ferroptosis |
| title_fullStr | Embryonal erythropoiesis and aging exploit ferroptosis |
| title_full_unstemmed | Embryonal erythropoiesis and aging exploit ferroptosis |
| title_short | Embryonal erythropoiesis and aging exploit ferroptosis |
| title_sort | embryonal erythropoiesis and aging exploit ferroptosis |
| topic | Ferroptosis Iron 4-Hydroxy-2-nonenal Erythropoiesis Aging |
| url | http://www.sciencedirect.com/science/article/pii/S2213231721003359 |
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