吲哚美辛诱导大鼠胃粘膜细胞凋亡过程中线粒体细胞色素c释放和caspase-3样蛋白酶激活。

Yasuyoshi Fujii, T. Matsura, M. Kai, Hirofumi Matsui, H. Kawasaki, Kazuo Yamada
{"title":"吲哚美辛诱导大鼠胃粘膜细胞凋亡过程中线粒体细胞色素c释放和caspase-3样蛋白酶激活。","authors":"Yasuyoshi Fujii, T. Matsura, M. Kai, Hirofumi Matsui, H. Kawasaki, Kazuo Yamada","doi":"10.1111/j.1525-1373.2000.22407.x","DOIUrl":null,"url":null,"abstract":"Indomethacin (IND), a nonsteroidal anti-inflammatory drug, has been known to cause gastric mucosal injury as a side effect. Using a rat gastric mucosal cell line, RGM1, we determined whether apoptosis is involved in IND-mediated gastropathy, and whether caspase activation and mitochondrial cytochrome c release play an important role in producing apoptosis of IND-treated RGM1 cells in the presence of serum. IND caused caspase-3-like protease activation followed by apoptosis in a dose- and time-dependent manner. Caspase-1-like protease activity did not change during IND-induced apoptosis. IND also increased mitochondrial cytochrome c release in a time-dependent fashion. Mitochondrial cytochrome c efflux occurred just before or at the same time as caspase-3-like protease activation, and preceded the increase in apoptotic cell numbers. Z-VAD-FMK, a caspase inhibitor, inhibited both the increase in caspase-3-like protease activity and apoptosis in IND-treated RGM1 cells but did not affect caspase-1-like protease activity or mitochondrial cytochrome c release. These observations suggest that the apoptosis of gastric mucosal cells could be involved in IND-induced gastropathy, that cytochrome c is released from mitochondria into the cytosol during the early phase of IND-mediated apoptosis, and that subsequent activation of caspase-3-like protease, but not caspase-1-like protease, is required for the execution of apoptosis.","PeriodicalId":20618,"journal":{"name":"Proceedings of the Society for Experimental Biology and Medicine. Society for Experimental Biology and Medicine","volume":"5 1","pages":"102-8"},"PeriodicalIF":0.0000,"publicationDate":"2000-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"27","resultStr":"{\"title\":\"Mitochondrial cytochrome c release and caspase-3-like protease activation during indomethacin-induced apoptosis in rat gastric mucosal cells.\",\"authors\":\"Yasuyoshi Fujii, T. Matsura, M. Kai, Hirofumi Matsui, H. Kawasaki, Kazuo Yamada\",\"doi\":\"10.1111/j.1525-1373.2000.22407.x\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"Indomethacin (IND), a nonsteroidal anti-inflammatory drug, has been known to cause gastric mucosal injury as a side effect. Using a rat gastric mucosal cell line, RGM1, we determined whether apoptosis is involved in IND-mediated gastropathy, and whether caspase activation and mitochondrial cytochrome c release play an important role in producing apoptosis of IND-treated RGM1 cells in the presence of serum. IND caused caspase-3-like protease activation followed by apoptosis in a dose- and time-dependent manner. Caspase-1-like protease activity did not change during IND-induced apoptosis. IND also increased mitochondrial cytochrome c release in a time-dependent fashion. Mitochondrial cytochrome c efflux occurred just before or at the same time as caspase-3-like protease activation, and preceded the increase in apoptotic cell numbers. Z-VAD-FMK, a caspase inhibitor, inhibited both the increase in caspase-3-like protease activity and apoptosis in IND-treated RGM1 cells but did not affect caspase-1-like protease activity or mitochondrial cytochrome c release. These observations suggest that the apoptosis of gastric mucosal cells could be involved in IND-induced gastropathy, that cytochrome c is released from mitochondria into the cytosol during the early phase of IND-mediated apoptosis, and that subsequent activation of caspase-3-like protease, but not caspase-1-like protease, is required for the execution of apoptosis.\",\"PeriodicalId\":20618,\"journal\":{\"name\":\"Proceedings of the Society for Experimental Biology and Medicine. Society for Experimental Biology and Medicine\",\"volume\":\"5 1\",\"pages\":\"102-8\"},\"PeriodicalIF\":0.0000,\"publicationDate\":\"2000-01-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"27\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Proceedings of the Society for Experimental Biology and Medicine. Society for Experimental Biology and Medicine\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.1111/j.1525-1373.2000.22407.x\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"\",\"JCRName\":\"\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Proceedings of the Society for Experimental Biology and Medicine. Society for Experimental Biology and Medicine","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1111/j.1525-1373.2000.22407.x","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
引用次数: 27

摘要

吲哚美辛(IND)是一种非甾体抗炎药,其副作用是引起胃粘膜损伤。利用大鼠胃粘膜细胞系RGM1,我们确定了凋亡是否参与了ind介导的胃病,以及在血清存在的情况下,半胱天冬酶激活和线粒体细胞色素c释放是否在ind处理的RGM1细胞产生凋亡中起重要作用。IND引起caspase-3样蛋白酶激活,随后出现剂量和时间依赖性的细胞凋亡。caspase -1样蛋白酶活性在ind诱导的细胞凋亡过程中未发生变化。IND还以时间依赖性的方式增加线粒体细胞色素c的释放。线粒体细胞色素c外排发生在caspase-3样蛋白酶激活之前或同时,并先于凋亡细胞数量的增加。caspase抑制剂Z-VAD-FMK可以抑制ind处理的RGM1细胞中caspase-3样蛋白酶活性和凋亡的增加,但不影响caspase-1样蛋白酶活性或线粒体细胞色素c的释放。这些观察结果表明,胃粘膜细胞的凋亡可能参与了ind诱导的胃病,细胞色素c在ind介导的凋亡的早期阶段从线粒体释放到细胞质中,随后的caspase-3样蛋白酶的激活,而不是caspase-1样蛋白酶的激活,是细胞凋亡的必要条件。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Mitochondrial cytochrome c release and caspase-3-like protease activation during indomethacin-induced apoptosis in rat gastric mucosal cells.
Indomethacin (IND), a nonsteroidal anti-inflammatory drug, has been known to cause gastric mucosal injury as a side effect. Using a rat gastric mucosal cell line, RGM1, we determined whether apoptosis is involved in IND-mediated gastropathy, and whether caspase activation and mitochondrial cytochrome c release play an important role in producing apoptosis of IND-treated RGM1 cells in the presence of serum. IND caused caspase-3-like protease activation followed by apoptosis in a dose- and time-dependent manner. Caspase-1-like protease activity did not change during IND-induced apoptosis. IND also increased mitochondrial cytochrome c release in a time-dependent fashion. Mitochondrial cytochrome c efflux occurred just before or at the same time as caspase-3-like protease activation, and preceded the increase in apoptotic cell numbers. Z-VAD-FMK, a caspase inhibitor, inhibited both the increase in caspase-3-like protease activity and apoptosis in IND-treated RGM1 cells but did not affect caspase-1-like protease activity or mitochondrial cytochrome c release. These observations suggest that the apoptosis of gastric mucosal cells could be involved in IND-induced gastropathy, that cytochrome c is released from mitochondria into the cytosol during the early phase of IND-mediated apoptosis, and that subsequent activation of caspase-3-like protease, but not caspase-1-like protease, is required for the execution of apoptosis.
求助全文
通过发布文献求助,成功后即可免费获取论文全文。 去求助
来源期刊
自引率
0.00%
发文量
0
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术官方微信