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  1. 020 学位論文
  2. 生命科学研究科
  3. 20 生理科学専攻

Roles of Disordered Volume Regulation in Apoptosis

https://ir.soken.ac.jp/records/1114
https://ir.soken.ac.jp/records/1114
bcd07695-1fee-4152-97f7-017aa7657fb6
名前 / ファイル ライセンス アクション
甲542_要旨.pdf 要旨・審査要旨 / Abstract, Screening Result (198.8 kB)
甲542_本文.pdf 本文 (2.4 MB)
Item type 学位論文 / Thesis or Dissertation(1)
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

前野, 恵美

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フリガナ マエノ, エミ

× マエノ, エミ

マエノ, エミ

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著者 MAENO, Emi

× MAENO, Emi

en 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)
学位記番号
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.
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内容記述 application/pdf
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