Daphnetin induces apoptosis in fibroblast-like synoviocytes from collagen-induced arthritic rats mainly via the mitochondrial pathway
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- 英文论文题名：Daphnetin induces apoptosis in fibroblast-like synoviocytes from collagen-induced arthritic rats mainly via the mitochondrial pathway
- 论文作者：Zheng Mao ; Kuang Nanzhen ; Zeng Xiaoping ; Wang Jieying ; Fu Yingyuan
- 英文论文作者：Zheng Mao ; Kuang Nanzhen ; Zeng Xiaoping ; Wang Jieying ; Fu Yingyuan ; Nanchang University
- 年：2016
- 作者机构：Nanchang University;
- 英文论文关键词：daphnetin ; FLSs ; apoptosis ; mitochondrial pathway
- 会议召开时间：2016-11-04
- 会议录名称：第十一届全国免疫学学术大会摘要汇编
- 英文会议录名称：Abstracts of 2016 CSI Congress on Immunology
- 语种：英文
- 分类号：R285.5
- 学会代码：IGMD
- 会议名称：第十一届全国免疫学学术大会
- 会议地点：中国安徽合肥
- 主办单位：中国免疫学会
- 学会名称：中国免疫学会
- 页数：1
- 文件大小：982k
- 原文格式：D
- 会议级别：全国
摘要
We have previously found that daphnetin(DAP) has a pro-apoptotic effect on fibroblast-like synoviocytes(FLSs) from collagen-induced arthritis(CIA) rats. In the present study, we further investigated the mechanism of DAP-induced apoptosis in CIA-FLSs. CIA-FLSs were incubated with DAP for 48 h in the presence or absence of caspase inhibitors, including inhibitors of caspase-3, caspase-8, or caspase-9 or a pan-caspase inhibitor; then, a series of experiments were performed to evaluate the mechanisms of DAP-induced apoptosis. Our results showed that DAP markedly decreased cell viability and induced the apoptosis of CIA-FLSs, along with typical morphological and ultrastructural changes; moreover, DAP increased the mRNA expression of Fas L, cytochrome c(Cyt-c), Bax, caspase-3, caspase-8, and caspase-9 and the protein expression of Bax, caspase-3, caspase-8, and caspase-9. In contrast, DAP decreased the mRNA and protein expression of Bcl-2 and promoted the release of Cyt-c from the mitochondria into the cytosol; these effects were attenuated to varying degrees by pre-treatment with caspase inhibitors, especially with caspase-3 or caspase-9 inhibitors or a pan-caspase inhibitor. In conclusion, the current findings demonstrate that the DAP-induced apoptosis of CIA-FLSs occurred mainly via a caspase-dependent pathway, in particular the mitochondrial pathway, and that the Bax/Bcl-2 ratio was involved in this process. Thus, DAP may be a potential therapeutic agent for RA.
We have previously found that daphnetin(DAP) has a pro-apoptotic effect on fibroblast-like synoviocytes(FLSs) from collagen-induced arthritis(CIA) rats. In the present study, we further investigated the mechanism of DAP-induced apoptosis in CIA-FLSs. CIA-FLSs were incubated with DAP for 48 h in the presence or absence of caspase inhibitors, including inhibitors of caspase-3, caspase-8, or caspase-9 or a pan-caspase inhibitor; then, a series of experiments were performed to evaluate the mechanisms of DAP-induced apoptosis. Our results showed that DAP markedly decreased cell viability and induced the apoptosis of CIA-FLSs, along with typical morphological and ultrastructural changes; moreover, DAP increased the mRNA expression of Fas L, cytochrome c(Cyt-c), Bax, caspase-3, caspase-8, and caspase-9 and the protein expression of Bax, caspase-3, caspase-8, and caspase-9. In contrast, DAP decreased the mRNA and protein expression of Bcl-2 and promoted the release of Cyt-c from the mitochondria into the cytosol; these effects were attenuated to varying degrees by pre-treatment with caspase inhibitors, especially with caspase-3 or caspase-9 inhibitors or a pan-caspase inhibitor. In conclusion, the current findings demonstrate that the DAP-induced apoptosis of CIA-FLSs occurred mainly via a caspase-dependent pathway, in particular the mitochondrial pathway, and that the Bax/Bcl-2 ratio was involved in this process. Thus, DAP may be a potential therapeutic agent for RA.
We have previously found that daphnetin(DAP) has a pro-apoptotic effect on fibroblast-like synoviocytes(FLSs) from collagen-induced arthritis(CIA) rats. In the present study, we further investigated the mechanism of DAP-induced apoptosis in CIA-FLSs. CIA-FLSs were incubated with DAP for 48 h in the presence or absence of caspase inhibitors, including inhibitors of caspase-3, caspase-8, or caspase-9 or a pan-caspase inhibitor; then, a series of experiments were performed to evaluate the mechanisms of DAP-induced apoptosis. Our results showed that DAP markedly decreased cell viability and induced the apoptosis of CIA-FLSs, along with typical morphological and ultrastructural changes; moreover, DAP increased the mRNA expression of Fas L, cytochrome c(Cyt-c), Bax, caspase-3, caspase-8, and caspase-9 and the protein expression of Bax, caspase-3, caspase-8, and caspase-9. In contrast, DAP decreased the mRNA and protein expression of Bcl-2 and promoted the release of Cyt-c from the mitochondria into the cytosol; these effects were attenuated to varying degrees by pre-treatment with caspase inhibitors, especially with caspase-3 or caspase-9 inhibitors or a pan-caspase inhibitor. In conclusion, the current findings demonstrate that the DAP-induced apoptosis of CIA-FLSs occurred mainly via a caspase-dependent pathway, in particular the mitochondrial pathway, and that the Bax/Bcl-2 ratio was involved in this process. Thus, DAP may be a potential therapeutic agent for RA.
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