• 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Medical Gas Research >Carbon monoxide inhibits Fas activating antibody-induced apoptosis in endothelial cells
【24h】

Carbon monoxide inhibits Fas activating antibody-induced apoptosis in endothelial cells

机译：一氧化碳抑制Fas激活抗体诱导的内皮细胞凋亡

获取原文
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

Background The extrinsic apoptotic pathway initiates when a death ligand, such as the Fas ligand, interacts with its cell surface receptor (ie., Fas/CD95), forming a death-inducing signaling complex (DISC). The Fas-dependent apoptotic pathway has been implicated in several models of lung or vascular injury. Carbon monoxide, an enzymatic product of heme oxygenase-1, exerts antiapoptotic effects at low concentration in vitro and in vivo. Methods Using mouse lung endothelial cells (MLEC), we examined the antiapoptotic potential of carbon monoxide against apoptosis induced by the Fas/CD95-activating antibody (Jo2). Carbon monoxide was applied to cell cultures in vitro. The expression and/or activation of apoptosis-related proteins and signaling intermediates were determined using Western Immunoblot and co-immunoprecipitation assays. Cell death was monitored by lactate dehydrogenase (LDH) release assays. Statistical significance was determined by student T-test and a value of P Results Treatment of MLEC with Fas-activating antibody (Jo2) induced cell death associated with the formation of the DISC, and activation of caspases (-8, -9, and -3), as well as the pro-apoptotic Bcl-2 family protein Bax. Exposure of MLEC to carbon monoxide inhibited Jo2-induced cell death, which correlated with the inhibition of DISC formation, cleavage of caspases-8, -9, and -3, and Bax activation. Carbon monoxide inhibited the phosphorylation of the Fas-associated death domain-containing protein, as well as its association with the DISC. Furthermore, carbon monoxide induced the expression of the antiapoptotic protein FLIP and increased its association with the DISC. CO-dependent cytoprotection against Fas mediated apoptosis in MLEC depended in part on activation of ERK1/2-dependent signaling. Conclusions Carbon monoxide has been proposed as a potential therapy for lung and other diseases based in part on its antiapoptotic effects in endothelial cells. In vitro, carbon monoxide may inhibit both Fas/caspase-8 and Bax-dependent apoptotic signaling pathways induced by Fas-activating antibody in endothelial cells. Strategies to block Fas-dependent apoptotic pathways may be useful in development of therapies for lung or vascular disorders.
机译：背景技术当死亡配体（例如Fas配体）与其细胞表面受体（即Fas / CD95）相互作用，形成诱导死亡的信号复合物（DISC）时，外部细胞凋亡途径就会启动。 Fas依赖的凋亡途径已涉及肺或血管损伤的几种模型。一氧化碳是血红素加氧酶-1的酶促产物，在体内和体外均以低浓度发挥抗凋亡作用。方法使用小鼠肺内皮细胞（MLEC）检测一氧化碳对Fas / CD95激活抗体（Jo2）诱导的凋亡的抗凋亡潜力。一氧化碳用于体外细胞培养。使用Western Immunoblot和免疫共沉淀测定法测定凋亡相关蛋白和信号传导中间体的表达和/或激活。通过乳酸脱氢酶（LDH）释放测定法监测细胞死亡。统计显着性由学生T检验和P值确定。结果用Fas激活抗体（Jo2）治疗MLEC可诱导与DISC形成相关的细胞死亡，并激活半胱氨酸蛋白酶（-8，-9和- 3）以及促凋亡的Bcl-2家族蛋白Bax。 MLEC暴露于一氧化碳可抑制Jo2诱导的细胞死亡，这与DISC形成的抑制，caspases-8，-9和-3的裂解以及Bax激活相关。一氧化碳抑制了Fas相关死亡域蛋白的磷酸化，以及与DISC的结合。此外，一氧化碳诱导抗凋亡蛋白FLIP的表达并增加其与DISC的结合。 MLEC中Fas介导的凋亡的CO依赖性细胞保护部分依赖于ERK1 / 2依赖性信号传导的激活。结论一氧化碳已被提议作为治疗肺部疾病和其他疾病的一种潜在疗法，部分原因是因为一氧化碳在内皮细​​胞中具有抗凋亡作用。在体外，一氧化碳可能同时抑制Fas / caspase-8和Fas活化抗体在内皮细胞中诱导的Bax依赖性凋亡信号通路。阻断Fas依赖性凋亡途径的策略可能在开发针对肺部或血管疾病的疗法中有用。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号