TRPV1 mediates cell death in rat synovial fibroblasts through calcium entry-dependent ROS production and mitochondrial depolarization
TRPV1 mediates cell death in rat synovial fibroblasts through calcium entry-dependent ROS production and mitochondrial depolarization
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DOI：
10.1016/j.bbrc.2008.02.155
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发表时间：
2008-05-16
影响因子：
3.1
通讯作者：
Yang, Wen Xiu
中科院分区：
文献类型：
--
作者：
Hu, Fen;Sun, Wen Wu;Yang, Wen Xiu
滑膜细胞增生是类风湿关节炎的关键，因此，潜在的治疗的重要目标。在这项工作中发现，TRPV 1激动剂辣椒素和酸性溶液（pH 5.5）诱导从胶原诱导的关节炎大鼠模型分离的滑膜细胞中细胞溶质钙浓度（[Ca 2 +]（c））和活性氧（ROS）产生的增加。在无钙缓冲液或TRPV 1拮抗剂辣椒平中，[Ca 2 +]（C）和ROS产生的增加完全消除。进一步的实验表明，辣椒素和pH 5.5的溶液引起线粒体膜去极化和细胞活力的降低，这种影响被辣椒平，或NAD（P）H氧化酶抑制剂diphenylene iodonium抑制。辣椒素和pH 5.5缓冲液诱导细胞凋亡所示的核凝聚和碎裂。RT-PCR检测到滑膜细胞TRPV 1 mRNA的表达。总之，这些数据表明TRPV 1激活通过[Ca 2 +]（c）升高、ROS产生和线粒体膜去极化触发滑膜细胞死亡。(C)2008年由Elsevier Inc.出版
Synoviocyte hyperplasia is critical for rheumatoid arthritis, therefore, potentially an important target for therapeutics. It was found in this work that a TRPV1 agonist capsaicin, and acidic solution (pH 5.5) induced increases in cytosolic calcium concentration ([Ca2+](c)) and reactive oxygen species (ROS) production in synoviocytes isolated from a rat model of collagen-induced arthritis. The increases in both [Ca2+](C) and ROS production were completely abolished in calcium-free buffer or by a TRPV1 antagonist capsazepine. Further experiments revealed that capsaicin and pH 5.5 solution caused mitochondrial membrane depolarization and reduction in cell viability; such effects were inhibited by capsazepine, or the NAD(P)H oxidase inhibitor diphenylene iodonium. Both capsaicin and pH 5.5 buffer induced apoptosis as shown by nuclear condensation and fragmentation. Furthermore, RT-PCR readily detected TRPV1 mRNA expression in the isolated synoviocytes. Taken together, these data indicated that TRPV1 activation triggered synoviocyte death by [Ca2+](c) elevation, ROS production, and mitochondrial membrane depolarization. (C) 2008 Published by Elsevier Inc.