Protease activity of procaspase-8 is essential for cell survival by inhibiting both apoptotic and nonapoptotic cell death dependent on receptor-interacting protein kinase 1 (RIP1) and RIP3.
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抄録
Caspase-8 has an important role as an initiator caspase during death receptor-mediated apoptosis. Moreover, it has been reported to contribute to the regulation of cell fate in various types of cells including T-cells. In this report, we show that caspase-8 has an essential role in cell survival in mouse T-lymphoma-derived L5178Y cells. The knockdown of caspase-8 expression decreased the growth rate and increased cell death, both of which were induced by the absence of protease activity of procaspase-8. The cell death was associated with reactive oxygen species (ROS) accumulation, caspase activation, and autophagosome formation. The cell death was inhibited completely by treatment with ROS scavengers, but only partly by treatment with caspase inhibitors, expression of Bcl-xL, and knockdown of caspase-3 or Atg-7 which completely inhibits apoptosis or autophagosome formation, respectively, indicating that apoptosis and autophagy-associated cell death are induced simultaneously by the knockdown of caspase-8 expression. Further analysis indicated that RIP1 and RIP3 regulate this multiple cell death, because the cell death as well as ROS production was completely inhibited by not only treatment with the RIP1 inhibitor necrostatin-1, but also by knockdown of RIP3. Thus, in the absence of protease activity of procaspase-8, RIP1 and RIP3 simultaneously induce not only nonapoptotic cell death conceivably including autophagic cell death and necroptosis but also apoptosis through ROS production in mouse T-lymphoma cells.
収録刊行物
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- The Journal of biological chemistry
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The Journal of biological chemistry 287 (49), 41165-41173, 2012-11-30
American Society for Biochemistry and Molecular Biology
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キーワード
- Apoptosis
- Autophagy
- Caspase
- Cell Death
- Necrosis (Necrotic Death)
- Reactive Oxygen Species (ROS)
- Necroptosis
- Animals
- Caspase 8/chemistry
- Caspase 8/metabolism
- Cell Line, Tumor
- Gene Expression Regulation, Enzymologic
- Humans
- Lymphoma, T-Cell/metabolism
- Mice
- Mice, Inbred BALB C
- Necrosis
- Nuclear Pore Complex Proteins/chemistry
- Peptide Hydrolases/chemistry
- RNA-Binding Proteins/chemistry
- Reactive Oxygen Species
- Receptor-Interacting Protein Serine-Threonine Kinases/chemistry
- T-Lymphocytes/metabolism
詳細情報 詳細情報について
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- CRID
- 1050282810760050688
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- NII論文ID
- 120005385882
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- NII書誌ID
- AA00251083
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- ISSN
- 00219258
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- HANDLE
- 2433/182923
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- 本文言語コード
- en
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- 資料種別
- journal article
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- データソース種別
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- IRDB
- CiNii Articles