ACROLEIN INDUCES NRF2 NUCLEAR TRANSLOCATION VIA TRPA1 CHANNEL ACTIVATION IN A549 CELLS

Introducion: Acrolein is present in cigarette smoke, vehicle exhaust, and air pollution. It has been reported that acrolein activates nuclear factor-erythroid 2 related factor2 (Nrf2) signaling pathway in lung epithelial cells. Acrolein is also known as one of transient receptor potential ankyrin-repeat 1 channel (TRPA1) agonists. However, the role of TRPA1 in the Nrf2 nuclear translocationMaterial and methods: In the present work, the change of Nrf2 nuclear translocation was analyzed by immunocytochemistry. At the same time, cytosolic Ca2+ concentration ([Ca2+]c) was examined in A549 cells stimulated by acrolein.Results: Results showed that Nrf2 nuclear translocation was enhanced by acrolein in A549 cells, which was abolished by AP18 (a TRPA1 channel blocker). In addition, AP-18 blocked enhanced [Ca2+]c induced by acrolein. The further experiments confirmed that removal of extracellular Ca2+ largely abrogated the [Ca2+]c elevation and nuclear translocation of Nrf2 induced by acroleinConclusions: Our results suggest that acrolein induces Nrf2 nuclear translocation through activation of TRPA1 in lung epithelial cells, which might be useful in the research and treatment of pulmonary disease.