TRPV1 stimulation triggers apoptotic cell death of rat cortical neurons
TRPV1 stimulation triggers apoptotic cell death of rat cortical neurons
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DOI：
10.1016/j.bbrc.2008.10.152
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发表时间：
2008-12-26
影响因子：
3.1
通讯作者：
Kaneko, Shuji
中科院分区：
文献类型：
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作者：
Shirakawa, Hisashi;Yamaoka, Tomoko;Kaneko, Shuji
瞬时受体电位香草酸 1 (TRPV1) 作为多模式伤害感受器发挥作用，并被多种香草酸激活，包括辣椒素、质子和听觉。尽管 TRPV1 通道广泛分布于大脑中，但其作用仍不清楚。在这里，我们使用表达 TRPV1 的培养大鼠皮层神经元研究了 TRPV1 在细胞毒性过程中的作用。辣椒素可诱导具有细胞凋亡特征的严重神经元死亡，这种死亡可被 TRPV1 拮抗剂辣椒西平完全抑制，并依赖于细胞外 Ca2+ 内流。有趣的是，硝苯地平（一种特定的 L 型 Ca2+ 通道阻滞剂）可减弱辣椒素的细胞毒性，即使在施用辣椒素 2-4 小时后也是如此。 ERK 抑制剂 PD98059 和几种抗氧化剂（但 JNK 和 p38 抑制剂）不会减弱辣椒素的细胞毒性。总之，这些数据表明 TRPV1 激活通过 L 型 Ca2+ 通道开放、Ca2+ 内流、ERK 磷酸化和活性氧产生触发大鼠皮质培养物的凋亡细胞死亡。 (C) 2008 Elsevier Inc. 保留所有权利。
Transient receptor potential vanilloid 1 (TRPV1) functions as a polymodal nociceptor and is activated by several vanilloids, including capsaicin, protons and hear. Although TRPV1 channels are widely distributed in the brain, their roles remain unclear. Here, we investigated the roles of TRPV1 in cytotoxic processes using TRPV1-expressing cultured rat cortical neurons. Capsaicin induced severe neuronal death with apoptotic features, which was completely inhibited by the TRPV1 antagonist capsazepine and was dependent oil extracellular Ca2+ influx. Interestingly, nifedipine, a specific L-type Ca2+ channel blocker, attenuated capsaicin cytotoxicity, even when applied 2-4 h after the capsaicin. ERK inhibitor PD98059 and several antioxidants, but not the JNK and p38 inhibitors, attenuated capsaicin cytotoxicity. Together, these data indicate that TRPV1 activation triggers apoptotic cell death of rat cortical cultures via L-type Ca2+ Channel opening, Ca2+ influx, ERK phosphorylation, and reactive oxygen species production. (C) 2008 Elsevier Inc. All rights reserved.