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Roles of Disordered Volume Regulation in Apoptosis
https://ir.soken.ac.jp/records/1114
https://ir.soken.ac.jp/records/1114bcd07695-1fee-4152-97f7-017aa7657fb6
名前 / ファイル | ライセンス | アクション |
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要旨・審査要旨 / Abstract, Screening Result (198.8 kB)
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本文 (2.4 MB)
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Item type | 学位論文 / Thesis or Dissertation(1) | |||||
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公開日 | 2010-02-22 | |||||
タイトル | ||||||
タイトル | Roles of Disordered Volume Regulation in Apoptosis | |||||
タイトル | ||||||
タイトル | Roles of Disordered Volume Regulation in Apoptosis | |||||
言語 | en | |||||
言語 | ||||||
言語 | eng | |||||
資源タイプ | ||||||
資源タイプ識別子 | http://purl.org/coar/resource_type/c_46ec | |||||
資源タイプ | thesis | |||||
著者名 |
前野, 恵美
× 前野, 恵美 |
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フリガナ |
マエノ, エミ
× マエノ, エミ |
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著者 |
MAENO, Emi
× MAENO, Emi |
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学位授与機関 | ||||||
学位授与機関名 | 総合研究大学院大学 | |||||
学位名 | ||||||
学位名 | 博士(理学) | |||||
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内容記述タイプ | Other | |||||
内容記述 | 総研大甲第542号 | |||||
研究科 | ||||||
値 | 生命科学研究科 | |||||
専攻 | ||||||
値 | 20 生理科学専攻 | |||||
学位授与年月日 | ||||||
学位授与年月日 | 2001-03-23 | |||||
学位授与年度 | ||||||
値 | 2000 | |||||
要旨 | ||||||
内容記述タイプ | Other | |||||
内容記述 | A major hallmark of apoptosis is normotonic shrinkage of cells. Here, we studied the relation between apoptotic cell shrinkage and apoptotic cell death. Induction of the apoptotic volume decrease (AVD) under normotonic conditions was found to be coupled to facilitation of the regulatory volume decrease (RVD), which is known to be attained by parallel operation of Cl<SUP>-</SUP> and K<SUP>+</SUP> channels, under hypotonic conditions. Both the AVD induction and the RVD facilitation were found to precede cytochrome c release, initiator caspase (-8, -9) activation, effector caspase (-3) activation, DNA laddering and ultrastructural alterations in four cell types (human lymphoid U937, epithelial HeLa, rat pheochromocytoma PC12 and mouse neuroblastoma X rat glioma hybrid NG108-15 cells) after apoptotic insults with two distinct apoptosis inducers. Also, the AVD was not prevented by a broad-spectrum caspase inhibitor. When the AVD induction and the RVD facilitation were prevented by blocking volume-regulatory Cl<SUP>-</SUP> or K<SUP>+</SUP> channels, these cells did not show succeeding apoptotic biochemical and morphological events and were rescued from death. Thus, it is concluded that the AVD, which is caused by disordered cell volume regulation, is an early prerequisite to apoptotic events leading to cell death. It was previously reported that hypertonic stress triggers apoptosis in cell types that lack the regulatory volume increase (RVI). In fact, in Na<SUP>+</SUP>/H<SUP>+</SUP> antiporter -deficient CCL39 cells, which were found to lack the RVI mechanism, hypertonic stimulation was found to induce persistent cell shrinkage without following volume recovery, and then lead to succeeding apoptotic events and cell death. When the RVI ability was conferred by transfection of the gene of NHE1 isoform of Na<SUP>+</SUP>/H<SUP>+</SUP> antiporter, this cell line failed to exhibit apoptosis under hypertonic stimulation. Taken together, it is concluded that disordered or altered cell volume regulation is a prerequisite to apoptosis. | |||||
所蔵 | ||||||
値 | 有 | |||||
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内容記述タイプ | Other | |||||
内容記述 | application/pdf |