Faculty of Pharmacy, Chiba Institute of Science, Choshi 288-0025, Japan.
Amine Pharma Research Institute, Innovation Plaza at Chiba University, Chiba 260-0856, Japan.
Int J Mol Sci. 2023 Jul 24;24(14):11847. doi: 10.3390/ijms241411847.
Transient receptor potential ankyrin 1 (TRPA1) is a nonselective ion channel implicated in thermosensation and inflammatory pain. It has been reported that expression of the TRPA1 channel is induced by cigarette smoke extract. Acrolein found in cigarette smoke is highly toxic and known as an agonist of the TRPA1 channel. However, the role of TRPA1 in the cytotoxicity of acrolein remains unclear. Here, we investigated whether the TRPA1 channel is involved in the cytotoxicity of acrolein in human lung cancer A549 cells. The IC of acrolein in A549 cells was 25 μM, and acrolein toxicity increased in a concentration- and time-dependent manner. When the effect of acrolein on TRPA1 expression was examined, the expression of TRPA1 in A549 cells was increased by treatment with 50 μM acrolein for 24 h or 500 μM acrolein for 30 min. AP-1, a transcription factor, was activated in the cells treated with 50 μM acrolein for 24 h, while induction of NF-κB and HIF-1α was observed in the cells treated with 500 μM acrolein for 30 min. These results suggest that acrolein induces TRPA1 expression by activating these transcription factors. Overexpression of TRPA1 in A549 cells increased acrolein sensitivity and the level of protein-conjugated acrolein (PC-Acro), while knockdown of TRPA1 in A549 cells or treatment with a TRPA1 antagonist caused tolerance to acrolein. These findings suggest that acrolein induces the TRPA1 channel and that an increase in TRPA1 expression promotes the cytotoxicity of acrolein.
瞬时受体电位锚蛋白 1（TRPA1）是一种非选择性离子通道，参与热感觉和炎性疼痛。据报道，TRPA1 通道的表达受香烟烟雾提取物诱导。香烟烟雾中发现的丙烯醛具有高度毒性，是 TRPA1 通道的激动剂。然而，TRPA1 在丙烯醛细胞毒性中的作用尚不清楚。在这里，我们研究了 TRPA1 通道是否参与人肺癌 A549 细胞中丙烯醛的细胞毒性。丙烯醛在 A549 细胞中的 IC为 25 μM，丙烯醛毒性呈浓度和时间依赖性增加。当研究丙烯醛对 TRPA1 表达的影响时，发现用 50 μM 丙烯醛处理 24 h 或 500 μM 丙烯醛处理 30 min 可增加 A549 细胞中 TRPA1 的表达。用 50 μM 丙烯醛处理 24 h 可激活细胞中的 AP-1（一种转录因子），而用 500 μM 丙烯醛处理 30 min 可诱导 NF-κB 和 HIF-1α的诱导。这些结果表明，丙烯醛通过激活这些转录因子诱导 TRPA1 表达。在 A549 细胞中过表达 TRPA1 增加了丙烯醛的敏感性和蛋白结合丙烯醛（PC-Acro）的水平，而在 A549 细胞中敲低 TRPA1 或用 TRPA1 拮抗剂处理会导致对丙烯醛的耐受性。这些发现表明，丙烯醛诱导 TRPA1 通道，TRPA1 表达的增加促进了丙烯醛的细胞毒性。
