2023 Fiscal Year Final Research Report
Analyses of the mechanism for the cell death of ring sideroblasts
| Project/Area Number |
21K06874
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Review Section |
Basic Section 49010:Pathological biochemistry-related
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| Research Institution | Iwate Medical University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
久保田 美子 岩手医科大学, 医学部, 准教授 (30260102)
金子 桐子 岩手医科大学, 医学部, 講師 (10545784)
鈴木 亘 岩手医科大学, 医学部, 助教 (90610395)
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| Project Period (FY) |
2021-04-01 – 2024-03-31
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| Keywords | 遺伝性鉄芽球性貧血 / 細胞死 / ferroptosis / 疾患モデル細胞 / ゲノム編集 |
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| Outline of Final Research Achievements |
Congenital sideroblastic anemia (CSA) is a relatively rare disorder characterized by the presence of ring sideroblasts in a patient's bone marrow. We have previously established the CSA model cells (HA2low cells) using cultured erythroblastoid cell lines in which the ALAS2 gene was mutated by genome editing method. Using HA2low cells, we have tried to examine the cause of cell death of erythroblasts in CSA patients. After the induction of erythroid differentiation, the rate of cell death in HA2low cells is more significant than that in wild-type cells. However, the increased rate of cell death in HA2low cells during erythroid differentiation was partially rescued by the treatment with the antagonist of ferroptosis, a kind of programmed cell death caused by the oxidative stress originated by the excess cellular iron accumulation. These results suggested that ferroptosis may be one of the causes of the increase of cell death in HA2low cells and anemia observed in CSA patients.
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| Free Research Field |
生化学、分子生物学
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| Academic Significance and Societal Importance of the Research Achievements |
遺伝性鉄芽球性貧血(CSA)は環状鉄芽球の出現を特徴とする疾患だが、環状鉄芽球の性質については不明な点が多い。本研究では、in vitroで環状鉄芽球の形成を誘導可能なモデル細胞を利用し、モデル細胞は細胞死を起こしやすい性質を有すること、その細胞死のうち少なくとも一部はferroptosis（過剰な鉄に起因する酸化ストレスが誘導する細胞死）による可能性が高いことを明らかにした。臨床的にCSA患者では鉄の過剰な蓄積が見られることが知られており、除鉄により貧血が改善する例も報告されているが、その理論的背景の説明に資する結果と考えている。
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