Department of Medical Biochemistry and Molecular Biology, Saarland University Medical Faculty, D-66421 Homburg, Germany.
Anatomy and Cell Biology, Saarland University Medical Faculty, D-66421 Homburg, Germany.
Biochem Pharmacol. 2018 Apr;150:160-169. doi: 10.1016/j.bcp.2018.02.008. Epub 2018 Feb 13.
Transient receptor potential vanilloid 1 (TRPV1) channels were originally described as the receptors of capsaicin, the main constituent of hot chili pepper. The biological functions of TRPV1 channels include pain sensation and inflammatory thermal hyperalgesia. Here, we show that stimulation of HEK293 cells expressing TRPV1 channels (H2C1 cells) with capsaicin or the TRPV1 ligand resiniferatoxin activated transcription mediated by the transcription factor AP-1. No cell death was occurring under these experimental conditions. The AP-1 activity was not altered in capsaicin or resiniferatoxin-stimulated HEK293 cells lacking TRPV1. We identified the AP-1 DNA binding site as the capsaicin/resiniferatoxin-responsive element. Stimulation with the TRPV1 ligand N-arachidonoyldopamine increased AP-1 activity in a TRPV1-dependent and TRPV1-independent manner. Stimulation of TRPV1 channels induced an influx of Ca into the cells and this rise in intracellular Ca was essential for activating AP-1 in capsaicin or resiniferatoxin-stimulated cells. N-arachidonoyldopamine stimulation induced a rise in intracellular Ca in a TRPV-1 dependent and independent manner. AP-1 is a dimeric transcription factor, composed of proteins of the c-Jun, c-Fos and ATF families. Stimulation of TRPV1 channels with capsaicin increased c-Jun and c-Fos biosynthesis in H2C1 cells. The signal transduction of capsaicin, leading to enhanced AP-1-mediated transcription, required extracellular signal-regulated protein kinase ERK1/2 as a signal transducer and the activation of the transcription factors c-Jun and ternary complex factor. Together, these data suggest that the intracellular functions of TRPV1 stimulation may rely on the activation of a stimulus-regulated protein kinase and stimulus-responsive transcription factors.
瞬时受体电位香草酸 1 型 (TRPV1) 通道最初被描述为辣椒素的受体，辣椒素是红辣椒的主要成分。TRPV1 通道的生物学功能包括疼痛感觉和炎症性热痛觉过敏。在这里，我们表明，用辣椒素或 TRPV1 配体树脂毒素刺激表达 TRPV1 通道的 HEK293 细胞 (H2C1 细胞) 会激活转录因子 AP-1 介导的转录。在这些实验条件下，没有发生细胞死亡。在缺乏 TRPV1 的辣椒素或树脂毒素刺激的 HEK293 细胞中，AP-1 活性没有改变。我们确定 AP-1 DNA 结合位点是辣椒素/树脂毒素反应元件。TRPV1 配体 N-花生四烯酰多巴胺的刺激以 TRPV1 依赖和 TRPV1 独立的方式增加了 AP-1 活性。TRPV1 通道的刺激导致 Ca 流入细胞内，这种细胞内 Ca 的增加对于激活辣椒素或树脂毒素刺激细胞中的 AP-1 是必不可少的。N-花生四烯酰多巴胺刺激以 TRPV-1 依赖和独立的方式诱导细胞内 Ca 的增加。AP-1 是一种二聚体转录因子，由 c-Jun、c-Fos 和 ATF 家族的蛋白质组成。用辣椒素刺激 TRPV1 通道增加了 H2C1 细胞中 c-Jun 和 c-Fos 的生物合成。导致增强的 AP-1 介导的转录的辣椒素信号转导需要细胞外信号调节蛋白激酶 ERK1/2 作为信号转导器，以及转录因子 c-Jun 和三元复合物因子的激活。总之，这些数据表明 TRPV1 刺激的细胞内功能可能依赖于激活刺激调节蛋白激酶和刺激反应转录因子。
