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

Zhang Jun-Li, Sun Wen-Wu, Cao Jian-Ping, Ma Zhuang^*

Department of Pulmonary and Critical Care Medicine, General Hospital of Northern Theater Command, Shenyang City, Liaoning Province, 110016, China

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 translocation caused by acrolein remains elusive.

Material 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 AP-18 (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 acrolein simultaneously.

Conclusions: 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.