Fine particulate matter exposure disturbs autophagy, redox balance and mitochondrial homeostasis via JNK activation to inhibit proliferation and promote EMT in human alveolar epithelial A549 cells
Epidemiologic studies have demonstrated a direct correlation between fine particulate matter (FPM) exposure and the high risk of respiratory diseases. FPM can penetrate deep into the lung and deposit in the alveoli with breath, where it directly interacts with alveolar epithelial cell (APC). However...
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| Format: | Article |
| Language: | English |
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Elsevier
2023-09-01
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| Series: | Ecotoxicology and Environmental Safety |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S0147651323006383 |
| _version_ | 1797744105926688768 |
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| author | Yan Wang Ying Li Yilin Gao Jiahao Kang Weijia Wang Yu-Le Yong Xiaoyan Qu Xiaomin Dang Dong Shang Yongping Shao Jiankang Liu Ying Chang Lin Zhao |
| author_facet | Yan Wang Ying Li Yilin Gao Jiahao Kang Weijia Wang Yu-Le Yong Xiaoyan Qu Xiaomin Dang Dong Shang Yongping Shao Jiankang Liu Ying Chang Lin Zhao |
| author_sort | Yan Wang |
| collection | DOAJ |
| description | Epidemiologic studies have demonstrated a direct correlation between fine particulate matter (FPM) exposure and the high risk of respiratory diseases. FPM can penetrate deep into the lung and deposit in the alveoli with breath, where it directly interacts with alveolar epithelial cell (APC). However, we know little about the effects nor mechanisms of FPM on APC. Here, using human APC A549 cells, we found that FPM resulted in blockade of autophagic flux, redox imbalance and oxidative stress, mitochondrial fragmentation, increased mitophagy and impaired mitochondrial respiration. Further we showed that activation of JNK signaling (c-Jun N-terminal kinase) and excessive ROS (reactive oxygen species) release contribute to these adverse effects, with the former being upstream of the latter. More importantly, we found that scavenging ROS or inhibiting JNK activation could restore those effects as well as ameliorate FPM-induced inhibition of cell proliferation, and epithelial-mesenchymal transformation (EMT) in A549 cells. Taken together, our findings indicate that FPM leads to toxicity in alveolar type II cells via JNK activation, and JNK-targeting or antioxidant strategies might be beneficial for prevention or treatment of FPM-related pulmonary diseases. |
| first_indexed | 2024-03-12T15:04:58Z |
| format | Article |
| id | doaj.art-031b3f6f51644241aa01a656b9c62ad5 |
| institution | Directory Open Access Journal |
| issn | 0147-6513 |
| language | English |
| last_indexed | 2024-03-12T15:04:58Z |
| publishDate | 2023-09-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Ecotoxicology and Environmental Safety |
| spelling | doaj.art-031b3f6f51644241aa01a656b9c62ad52023-08-13T04:51:43ZengElsevierEcotoxicology and Environmental Safety0147-65132023-09-01262115134Fine particulate matter exposure disturbs autophagy, redox balance and mitochondrial homeostasis via JNK activation to inhibit proliferation and promote EMT in human alveolar epithelial A549 cellsYan Wang0Ying Li1Yilin Gao2Jiahao Kang3Weijia Wang4Yu-Le Yong5Xiaoyan Qu6Xiaomin Dang7Dong Shang8Yongping Shao9Jiankang Liu10Ying Chang11Lin Zhao12Center for Mitochondrial Biology and Medicine, The Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology and Frontier Institute of Science and Technology, Xi'an Jiaotong University, Xi'an, Shaanxi province, ChinaDepartment of Dermatology, The Second Affiliated Hospital, School of Medicine, Xi'an Jiaotong University, Xi'an, Shaanxi province, ChinaCenter for Mitochondrial Biology and Medicine, The Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology and Frontier Institute of Science and Technology, Xi'an Jiaotong University, Xi'an, Shaanxi province, ChinaCenter for Mitochondrial Biology and Medicine, The Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology and Frontier Institute of Science and Technology, Xi'an Jiaotong University, Xi'an, Shaanxi province, ChinaCenter for Translational Medicine, The Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology and Frontier Institute of Science and Technology, Xi'an Jiaotong University, Xi'an, Shaanxi province, ChinaNational Translational Science Center for Molecular Medicine, Department of Cell Biology, Fourth Military Medical University, Xi'an, Shaanxi province, ChinaCenter for Translational Medicine, The Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology and Frontier Institute of Science and Technology, Xi'an Jiaotong University, Xi'an, Shaanxi province, ChinaDepartment of Respiration, The First Affiliated Hospital, Xi’an Jiaotong University, Xi’an, Shaanxi province, ChinaDepartment of Respiration, The First Affiliated Hospital, Xi’an Jiaotong University, Xi’an, Shaanxi province, ChinaCenter for Translational Medicine, The Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology and Frontier Institute of Science and Technology, Xi'an Jiaotong University, Xi'an, Shaanxi province, ChinaCenter for Mitochondrial Biology and Medicine, The Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology and Frontier Institute of Science and Technology, Xi'an Jiaotong University, Xi'an, Shaanxi province, China; School of Life Sciences, University of Health and Rehabilitation Sciences, Qingdao 266071, ChinaCenter for Translational Medicine, The Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology and Frontier Institute of Science and Technology, Xi'an Jiaotong University, Xi'an, Shaanxi province, China; Correspondence to: Center for Translational Medicine, The Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology and Frontier Institute of Science and Technology, Xi'an Jiaotong University, No.28 Road Xianningxi, Xi'an, Shaanxi province 710049, China.Center for Mitochondrial Biology and Medicine, The Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology and Frontier Institute of Science and Technology, Xi'an Jiaotong University, Xi'an, Shaanxi province, China; Correspondence to: Center for Mitochondrial Biology and Medicine, The Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology and Frontier Institute of Science and Technology, Xi'an Jiaotong University, No.28 Road Xianningxi, Xi'an 710049, China.Epidemiologic studies have demonstrated a direct correlation between fine particulate matter (FPM) exposure and the high risk of respiratory diseases. FPM can penetrate deep into the lung and deposit in the alveoli with breath, where it directly interacts with alveolar epithelial cell (APC). However, we know little about the effects nor mechanisms of FPM on APC. Here, using human APC A549 cells, we found that FPM resulted in blockade of autophagic flux, redox imbalance and oxidative stress, mitochondrial fragmentation, increased mitophagy and impaired mitochondrial respiration. Further we showed that activation of JNK signaling (c-Jun N-terminal kinase) and excessive ROS (reactive oxygen species) release contribute to these adverse effects, with the former being upstream of the latter. More importantly, we found that scavenging ROS or inhibiting JNK activation could restore those effects as well as ameliorate FPM-induced inhibition of cell proliferation, and epithelial-mesenchymal transformation (EMT) in A549 cells. Taken together, our findings indicate that FPM leads to toxicity in alveolar type II cells via JNK activation, and JNK-targeting or antioxidant strategies might be beneficial for prevention or treatment of FPM-related pulmonary diseases.http://www.sciencedirect.com/science/article/pii/S0147651323006383FPMLC3IIROSMitochondrial fragmentationOxygen consumption rate |
| spellingShingle | Yan Wang Ying Li Yilin Gao Jiahao Kang Weijia Wang Yu-Le Yong Xiaoyan Qu Xiaomin Dang Dong Shang Yongping Shao Jiankang Liu Ying Chang Lin Zhao Fine particulate matter exposure disturbs autophagy, redox balance and mitochondrial homeostasis via JNK activation to inhibit proliferation and promote EMT in human alveolar epithelial A549 cells Ecotoxicology and Environmental Safety FPM LC3II ROS Mitochondrial fragmentation Oxygen consumption rate |
| title | Fine particulate matter exposure disturbs autophagy, redox balance and mitochondrial homeostasis via JNK activation to inhibit proliferation and promote EMT in human alveolar epithelial A549 cells |
| title_full | Fine particulate matter exposure disturbs autophagy, redox balance and mitochondrial homeostasis via JNK activation to inhibit proliferation and promote EMT in human alveolar epithelial A549 cells |
| title_fullStr | Fine particulate matter exposure disturbs autophagy, redox balance and mitochondrial homeostasis via JNK activation to inhibit proliferation and promote EMT in human alveolar epithelial A549 cells |
| title_full_unstemmed | Fine particulate matter exposure disturbs autophagy, redox balance and mitochondrial homeostasis via JNK activation to inhibit proliferation and promote EMT in human alveolar epithelial A549 cells |
| title_short | Fine particulate matter exposure disturbs autophagy, redox balance and mitochondrial homeostasis via JNK activation to inhibit proliferation and promote EMT in human alveolar epithelial A549 cells |
| title_sort | fine particulate matter exposure disturbs autophagy redox balance and mitochondrial homeostasis via jnk activation to inhibit proliferation and promote emt in human alveolar epithelial a549 cells |
| topic | FPM LC3II ROS Mitochondrial fragmentation Oxygen consumption rate |
| url | http://www.sciencedirect.com/science/article/pii/S0147651323006383 |
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