Role of non-neuronal cholinergic system in the early stage response of epithelial-mesenchymal transformation related markers in A549 cells induced by coal particles
Meng-Yu Wu,
Xin-Chen Shi,
Jing Shan,
Rui Wang,
Yi Wang,
Jie Li,
Da-Nian Tian,
Hai-Ming Xu
Affiliations
Meng-Yu Wu
School of Public Health and Management, Ningxia Medical University, Yinchuan 750004, Ningxia, China; The Key Laboratory of Environmental Factors and Chronic Disease Control of Ningxia, No. 1160, Shengli Street, Xingqing District, Yinchuan, Ningxia, China
Xin-Chen Shi
School of Public Health and Management, Ningxia Medical University, Yinchuan 750004, Ningxia, China; The Key Laboratory of Environmental Factors and Chronic Disease Control of Ningxia, No. 1160, Shengli Street, Xingqing District, Yinchuan, Ningxia, China
Jing Shan
School of Public Health and Management, Ningxia Medical University, Yinchuan 750004, Ningxia, China; The Key Laboratory of Environmental Factors and Chronic Disease Control of Ningxia, No. 1160, Shengli Street, Xingqing District, Yinchuan, Ningxia, China
Rui Wang
School of Public Health and Management, Ningxia Medical University, Yinchuan 750004, Ningxia, China; The Key Laboratory of Environmental Factors and Chronic Disease Control of Ningxia, No. 1160, Shengli Street, Xingqing District, Yinchuan, Ningxia, China
Yi Wang
School of Public Health and Management, Ningxia Medical University, Yinchuan 750004, Ningxia, China; The Key Laboratory of Environmental Factors and Chronic Disease Control of Ningxia, No. 1160, Shengli Street, Xingqing District, Yinchuan, Ningxia, China
Jie Li
School of Public Health and Management, Ningxia Medical University, Yinchuan 750004, Ningxia, China; The Key Laboratory of Environmental Factors and Chronic Disease Control of Ningxia, No. 1160, Shengli Street, Xingqing District, Yinchuan, Ningxia, China
Da-Nian Tian
School of Public Health and Management, Ningxia Medical University, Yinchuan 750004, Ningxia, China; The Key Laboratory of Environmental Factors and Chronic Disease Control of Ningxia, No. 1160, Shengli Street, Xingqing District, Yinchuan, Ningxia, China; Corresponding author.
Hai-Ming Xu
School of Public Health and Management, Ningxia Medical University, Yinchuan 750004, Ningxia, China; The Key Laboratory of Environmental Factors and Chronic Disease Control of Ningxia, No. 1160, Shengli Street, Xingqing District, Yinchuan, Ningxia, China; Corresponding author.
Objective: This study was aimed to investigate the role of non-neuronal cholinergic system (NNCS) in the early stage response of epithelial-mesenchymal transformation (EMT) related markers in human lung adenocarcinoma A549 cells induced by coal particles. Methods: A549 cells were exposed to different concentrations of GBW11110K, GBW11126D and exogenous acetylcholinesterase (AChE) (the exposure doses were determined according to the results of CCK-8 experiment, and the doses that had no significant effects on cell viability were selected) for 24 h. After exposure, the indexes of oxidative stress (SOD and MDA), inflammatory factors (IL-6 and TNF-α), EMT marker proteins (E-cadherin and vimentin), AChE enzymatic activity and mRNA expression levels of different types of acetylcholine receptors (CHRM3, CHRM5, CHRNA5, CHRNA7, CHRNA9 and CHRNB2) were determined. Results: GBW11110K and GBW11126D exposure could lead to the following injury effects: the levels of oxidative stress and inflammatory factors changed to a certain extent (SOD decreased gradually, while MDA, IL-6 and TNF-α increased). The protein level of E-cadherin decreased while the vimentin level increased (P < 0.05), suggesting the occurrence of EMT. The AChE enzymatic activity decreased gradually. The expression of acetylcholine receptor mRNA changed as follows (GBW11110K/GBW11126D: CHRM3 (↑↑), CHRM5 (↓↓), CHRNA5 (↓↓), CHRNA7 (↓↓), CHRNA9 (– ↑), CHRNB2 (– –). The addition of exogenous AChE recombinant protein could antagonize the damage effects caused by the coal particles to a certain extent. Conclusion: The coal particle exposure could induce the change of oxidative stress response, inflammatory response and EMT related markers, down-regulate the AChE enzymatic activity, and interfere the mRNA expression levels of AChRs in A549 cells. The addition of exogenous AChE recombinant protein could reverse the above effects to a certain extent.
