Paclitaxel (PTX) is a frequently used anticancer drug that causes peripheral neuropathy. Transient receptor potential ankyrin 1 (TRPA1), a plasma membrane calcium channel, has been associated with PTX toxicity and with other chemotherapy agents such as oxaliplatin and vincristine. However, the effect of PTX on the functional expression and calcium currents of TRPA1 has not been determined. The present study shows the effect of PTX on TRPA1 activity in a neuronal cell line (SH-SY5Y). The effect of PTX on the expression of TRPA1 was assessed through quantitative PCR and Western blot analyses to determine the relative mRNA and protein expression levels. To assess the effect on calcium flux and currents, cells were exposed to PTX; simultaneously, a specific agonist and antagonist of TRPA1 were added to evaluate the differential response in exposed versus control cells. To assess the effect of PKA, PKC and PI3K on PTX-induced TRPA1 increased activity, selective inhibitors were added to these previous experiments. PTX increased the mRNA and protein expression of TRPA1 as well as the TRPA1-mediated Ca²⁺ currents and intracellular Ca²⁺ concentrations. This effect was dependent on AITC (a selective specific agonist) and was abolished with HC-030031 (a selective specific antagonist). The inhibition of PKA and PKC reduced the effect of PTX on the functional expression of TRPA1, whereas the inhibition of PI3K had no effects. PTX-induced neuropathy involves TRPA1 activity through an increase in functional expression and is regulated by PKA and PKC signaling. These findings support the role of the TRPA1 channel in the mechanisms altered by PTX, which can be involved in the process that lead to chemotherapy-induced neuropathy.

紫杉醇 (PTX) 是一种常用的抗癌药物，可引起周围神经病变。瞬时受体电位锚蛋白 1 (TRPA1) 是一种质膜钙通道，与 PTX 毒性以及其他化疗药物（如奥沙利铂和长春新碱）有关。然而，PTX 对 TRPA1 功能表达和钙电流的影响尚未确定。本研究显示 PTX 对神经元细胞系 (SH-SY5Y) 中 TRPA1 活性的影响。通过定量 PCR 和蛋白质印迹分析评估 PTX 对 TRPA1 表达的影响，以确定相对 mRNA 和蛋白质表达水平。为了评估对钙通量和电流的影响，将细胞暴露于 PTX；同时，添加 TRPA1 的特定激动剂和拮抗剂，以评估暴露细胞与对照细胞的差异反应。为了评估 PKA、PKC 和 PI3K 对 PTX 诱导的 TRPA1 活性增加的影响，在之前的实验中添加了选择性抑制剂。 PTX 增加 TRPA1 的 mRNA 和蛋白表达以及 TRPA1 介导的 Ca ²⁺电流和细胞内 Ca ²⁺浓度。这种作用依赖于 AITC（一种选择性特异性激动剂），并被 HC-030031（一种选择性特异性拮抗剂）消除。 PKA和PKC的抑制降低了PTX对TRPA1功能表达的影响，而PI3K的抑制则没有影响。 PTX 诱导的神经病变通过功能表达增加涉及 TRPA1 活性，并受 PKA 和 PKC 信号传导调节。这些发现支持 TRPA1 通道在 PTX 改变机制中的作用，PTX 可能参与导致化疗引起的神经病变的过程。