Selectively Induced Apoptosis in Human Neutrophils in the Presence of Oxidative Phenoxazines, 2-Amino-4,4α-dihydryo-4α-7H-phenoxazine-3-one and 2-Aminophenoxazine-3-one, Preceded by Decrease of Intracellular pH, Depolarization of the Mitochondria, and Inhibition of Superoxide Generation
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- Tabuchi Takanobu
- Fourth Department of Surgery, Tokyo Medical University, Ibaraki Medical Center, Japan
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- Che Xiao-Fang
- Department of Biochemistry, Tokyo Medical University, Japan
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- Hiraishi Katsuya
- AdaBio Co., Ltd., Japan
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- Adachi Masakazu
- AdaBio Co., Ltd., Japan
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- Miyano Kei
- Department of Biochemistry, Kyushu University Graduate School of Medical Sciences, Japan
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- Sumimoto Hideki
- Department of Biochemistry, Kyushu University Graduate School of Medical Sciences, Japan
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- Tabuchi Takafumi
- Fourth Department of Surgery, Tokyo Medical University, Ibaraki Medical Center, Japan
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- Miyazawa Keisuke
- Department of Biochemistry, Tokyo Medical University, Japan
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- Tomoda Akio
- Department of Biochemistry, Tokyo Medical University, Japan
書誌事項
- タイトル別名
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- Selectively Induced Apoptosis in Human Neutrophils in the Presence of Oxidative Phenoxazines, 2-Amino-4,4<I>α</I>-dihydryo-4<I>α</I>-7<I>H</I>-phenoxazine-3-one and 2-Aminophenoxazine-3-one, Preceded by Decrease of Intracellular pH, Depolarization of the Mitochondria, and Inhibition of Superoxide Generation
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抄録
The present research investigated the effect of the oxidative phenoxazines, 2-amino-4,4α-dihydryo-4α-7H-phenoxazine-3-one (Phx-1) and 2-amino-phenoxazine-3-one (Phx-3) on apoptosis induction and apoptosis-related early events in human neutrophils. When Phx-1 or Phx-3 was administered to freshly drawn human blood for 18 h, these phenoxazines caused apoptotic cell death morphologically characterized by condensation of the nucleus in neutrophils, without causing it in lymphocytes and monocytes. Apoptosis, which was detectable by microscopic analysis and by using flow-cytometry, occurred significantly in human neutrophils isolated from freshly drawn blood, 6 h after the administration of 50 μM Phx-1 and Phx-3. After 24 h, every isolated neutrophil treated with Phx-1 or Phx-3 fell into apoptosis or lost its morphology, while many of the neutrophils without these phenoxazines remained alive, with normal morphology. Apoptosis-related early events including a decrease in intracellular pH (pHi) and depolarization of the mitochondria occurred in the isolated neutrophils, 30 min and 6 h after the administration of Phx-1 or Phx-3, respectively. Superoxide generation from the isolated neutrophils mimicked by phorbol myristate acetate (PMA) was very markedly inhibited by 100 μM Phx-1 or Phx-3. This result could be explained, in part, by the fact that the insufficient supply of NADPH (nicotinamide adenine dinucleotide phosphate, reduced form) was caused by pHi decrease in neutrophils treated with Phx-1 or Phx, because NADPH is necessary for NADPH oxidase responsible for generating superoxide in the cells. The present results suggest that Phx-1 and Phx-3 have the capacity of selectively inducing apoptosis in human neutrophils and that these phenoxazines may be useful as specific drugs to induce apoptotic cell death of human neutrophils and thereby prevent inflammation caused by these phagocytic cells.
収録刊行物
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- Journal of Pharmacological Sciences
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Journal of Pharmacological Sciences 117 (3), 139-148, 2011
公益社団法人 日本薬理学会
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詳細情報 詳細情報について
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- CRID
- 1390282680154860288
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- NII論文ID
- 10030453178
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- NII書誌ID
- AA11806667
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- ISSN
- 13478648
- 13478613
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- NDL書誌ID
- 023319995
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- 本文言語コード
- en
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- データソース種別
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- JaLC
- NDL
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