cFLIP Regulates Death Receptor mediated Apoptosis in an Ovarian Granulosa Cell Line by Inhibiting Procaspase-8 Cleavage
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概要
- 論文の詳細を見る
More than 99% of follicles in mammalian ovaries undergo atresia, but the mechanisms regulating the strict selection process are still unclear. Granulosa cell apoptosis is considered the trigger of follicular atresia, which occurs in advance of the death of an oocyte. Cellular FLICE-like inhibitory protein (cFLIP), a homologue of procaspase-8 (also called FLICE), is an intracellular anti-apoptotic protein. It is expressed in granulosa cells of porcine ovaries, where its levels decreases during follicular atresia. We hypothesized that cFLIP regulates granulosa cell apoptosis by acting as a pro-survival factor. In the present study, to further reveal the function of cFLIP in granulosa cells, we examined the anti-apoptotic mechanism of cFLIP using KGN, a human granulosa tumor cell line. Fas-mediated apoptosis was induced by co-treatment with anti-Fas antibody (CH-11), which acts as an agonist of Fas-ligand, and cycloheximide (CHX). When cFLIP was stably expressed in KGN cells following transfection of an expression vector, the Fas-mediated apoptosis was inhibited. Suppression of cFLIP by small interfering RNA (siRNA) spontaneously induced cell death. Silencing of cFLIP promoted cleavage of procaspase-8, and the cell death caused by cFLIP siRNA was completely blocked by a caspase-8 inhibitor (Z-IETD-FMK), indicating that cFLIP regulates apoptosis in KGN cells by inhibiting cleavage of procaspase-8. In conclusion, cFLIP is an essential pro-survival factor for granulosa cells, and it prevents granulosa cell apoptosis by inhibiting procaspase-8 activation.
- 日本繁殖生物学会の論文
- 2008-10-01
著者
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MANABE Noboru
Research Unit of Animal Life Sciences, Animal Resource Science Centre, The University of Tokyo
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Inoue Naoko
Laboratory Of Animal Morphology And Function Graduate School Of Bioagricultural Sciences Nagoya Univ
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MAEDA Akihisa
Research Unit for Animal Life Sciences, Animal Resource Science Center, The University of Tokyo
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SAKAMAKI Kazuhiro
Laboratory of Tumore Cell Biology, Department of Life Sciences, Kyoto University
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Manabe Noboru
Graduate School Of Agricultural And Life Sciences Univ. Of Tokyo
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Manabe Noboru
Graduate School Of Agricultural And Life Sciences University Of Tokyo
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Manabe Noboru
Animal Resource Science Center Graduated School Of Agriculture And Life Science University Of Tokyo
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Manabe Noboru
Animal Resource Science Center The University Of Tokyo
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MAEDA Akihisa
Animal Resource Science Center, The University of Tokyo
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GOTO Yasufumi
Animal Resource Science Center, The University of Tokyo
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MATSUDA Fuko
Research Unit for Animal Life Sciences, Animal Resource Science Center, Graduate School of Agricultu
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GOTO Yasufumi
Research Unit for Animal Life Sciences, Animal Resource Science Center, Graduate School of Agricultu
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CHENG Yuan
Research Unit for Animal Life Sciences, Animal Resource Science Center, Graduate School of Agricultu
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Sakamaki Kazuhiro
Laboratory Of Tumor Cell Biology Department Of Life Sciences Kyoto University
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Sakamaki Kazuhiro
Graduate School Of Biostudies And Institute For Virus Research Kyoto University
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Sakamaki Kazuhiro
Laboratory Of Developmental Cell Biology Division Of Systemic Life Science Graduate School Of Biostu
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Cheng Yuan
Animal Resource Science Center The University Of Tokyo
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Matsuda Fuko
東京大学大学院農学生命科学研究科高等動物教育研究センター附属牧場
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Manabe Noboru
Animal Resource Sci. Center Graduate School Of Agricultural And Life Sciences The Univ. Of Tokyo
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Matsuda F
Univ. Tokyo Tokyo Jpn
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Inoue Naoko
Unit Of Anatomy And Cell Biology Department Of Animal Sciences Kyoto University
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Manabe Noboru
Research Center For Food Safety Graduate School Of Agricultural And Life Sciences The University Of
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Maeda Akihisa
Research Unit For Animal Life Sciences Animal Resource Science Center Graduate School Of Agricultura
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Goto Yasufumi
Research Unit For Animal Life Sciences Animal Resource Science Center Graduate School Of Agricultura
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Matsuda-minehata Fuko
Research Unit For Animal Life Sciences Animal Resource Science Center Graduate School Of Agricultura
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Cheng Yuan
Research Unit For Animal Life Sciences Animal Resource Science Center Graduate School Of Agricultura
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Inoue Naoko
Laboratory Of Animal Morphology And Function Division Of Biofunctional Development Graduate School Of Bioagricultural Sciences Nagoya University
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