A [Lys49]phospholipase A2 from Protobothrops flavoviridis Venom Induces Caspase-Independent Apoptotic Cell Death Accompanied by Rapid Plasma-Membrane Rupture in Human Leukemia Cells
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概要
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Protobothrops flavoviridis venom contains plural phospholipase A2 (PLA2) isozymes. A [Lys49]PLA2 called BPII induced cell death in human leukemia cells. PLA2, an [Asp49]PLA2 that has much stronger lipolytic activity than BPII, failed to induce cell death. BPII-treated cells showed morphological changes, DNA fragmentation, and nuclear condensation. This BPII-induced apoptotic cell death was neither inhibited by inhibitors of caspases 3 and 6 nor accompanied by activation of procaspase 3, indicating that BPII-induced cell death is caspase independent. Since inactive p-bromophenacylated BPII induced cell death, BPII-induced apoptotic cell death is independent of PLA2 lipolytic activity. Rapid externalization of phosphatidylserine in BPII-treated cells was observed for fluorescein isothiocyanate (FITC)-labeled annexin V. In the cells treated with BPII, this spread over the cell membranes, implying that the cell toxicity of BPII is mediated via its cell-surface receptor.
著者
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OHNO Motonori
Department of Applied Microbial Technology, Kumamoto Institute of Technology
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Nakamura Hitomi
Laboratory of Minamata Environmental Research and Develop Center Co., LTD.
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MURAKAMI Tatsuo
Department of Anesthesia, Gifu Red Cross Hospital
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KAMIKADO Nobuyuki
Department of Applied Microbial Technology, Faculty of Bioscience and Biotechnology, Sojo University
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FUJIMOTO Ryo
Department of Applied Microbial Technology, Faculty of Bioscience and Biotechnology, Sojo University
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HAMAGUCHI Kazuhiko
Department of Applied Microbial Technology, Faculty of Bioscience and Biotechnology, Sojo University
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CHIJIWA Takahito
Department of Applied Life Science, Faculty of Bioscience and Biotechnology, Sojo University
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ODA-UEDA Naoko
Laboratory of Biological Chemistry, Department of Pharmaceutical Sciences, Faculty of Pharmaceutical
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