Polyhexamethylene guanidine phosphate increases stress granule formation in human 3D lung organoids under respiratory syncytial virus infection
Polyhexamethylene guanidine phosphate (PHMG-p), a humidifier disinfectant, is known to cause lung toxicity, including inflammation and pulmonary fibrosis. In this study, we aimed to investigate the effect of PHMG-p on human lung tissue models (2D epithelial cells and 3D organoids) under conditions o...
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| Format: | Article |
| Language: | English |
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Elsevier
2022-01-01
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| Series: | Ecotoxicology and Environmental Safety |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S0147651321012069 |
| _version_ | 1798026741823832064 |
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| author | Seri Choi Sunkyung Choi Yeongsoo Choi Namjoon Cho Seung-Yeon Kim Chang Hyun Lee Han-Jin Park Won Keun Oh Kee K. Kim Eun-Mi Kim |
| author_facet | Seri Choi Sunkyung Choi Yeongsoo Choi Namjoon Cho Seung-Yeon Kim Chang Hyun Lee Han-Jin Park Won Keun Oh Kee K. Kim Eun-Mi Kim |
| author_sort | Seri Choi |
| collection | DOAJ |
| description | Polyhexamethylene guanidine phosphate (PHMG-p), a humidifier disinfectant, is known to cause lung toxicity, including inflammation and pulmonary fibrosis. In this study, we aimed to investigate the effect of PHMG-p on human lung tissue models (2D epithelial cells and 3D organoids) under conditions of oxidative stress and viral infection. The effect of PHMG-p was studied by evaluating the formation of stress granules (SGs), which play a pivotal role in cellular adaptation to various stress conditions. Under oxidative stress and respiratory syncytial virus (RSV) infection, exposure to PHMG-p remarkably increased eIF2α phosphorylation, which is essential for SG-related signalling, and significantly increased SG formation. Furthermore, PHMG-p induced fibrotic gene expression and caused cell death due to severe DNA damage, which was further increased under oxidative stress and RSV infection, indicating that PHMG-p induces severe lung toxicity under stress conditions. Taken together, toxicity evaluation under various stressful conditions is necessary to accurately predict potential lung toxicity of chemicals affecting the respiratory tract. |
| first_indexed | 2024-04-11T18:40:17Z |
| format | Article |
| id | doaj.art-f51809bd776646929942a4d328e39ca6 |
| institution | Directory Open Access Journal |
| issn | 0147-6513 |
| language | English |
| last_indexed | 2024-04-11T18:40:17Z |
| publishDate | 2022-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Ecotoxicology and Environmental Safety |
| spelling | doaj.art-f51809bd776646929942a4d328e39ca62022-12-22T04:09:02ZengElsevierEcotoxicology and Environmental Safety0147-65132022-01-01229113094Polyhexamethylene guanidine phosphate increases stress granule formation in human 3D lung organoids under respiratory syncytial virus infectionSeri Choi0Sunkyung Choi1Yeongsoo Choi2Namjoon Cho3Seung-Yeon Kim4Chang Hyun Lee5Han-Jin Park6Won Keun Oh7Kee K. Kim8Eun-Mi Kim9Department of Predictive Toxicology, Korea Institute of Toxicology, Daejeon 34114, South Korea; Korea Bioactive Natural Material Bank, Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Seoul 08826, South KoreaDepartment of Biochemistry, Chungnam National University, Daejeon 34134, South KoreaDepartment of Biochemistry, Chungnam National University, Daejeon 34134, South KoreaDepartment of Biochemistry, Chungnam National University, Daejeon 34134, South KoreaDepartment of Predictive Toxicology, Korea Institute of Toxicology, Daejeon 34114, South Korea; Department of Biochemistry, Chungnam National University, Daejeon 34134, South KoreaInstitute of Radiation Medicine, Seoul National University Hospital and College of Medicine, Seoul National University, Seoul 08826, South Korea; Department of Radiology, Seoul National University College of Medicine and Hospital, Seoul National University, Seoul 03080, South KoreaDepartment of Predictive Toxicology, Korea Institute of Toxicology, Daejeon 34114, South KoreaKorea Bioactive Natural Material Bank, Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Seoul 08826, South KoreaDepartment of Biochemistry, Chungnam National University, Daejeon 34134, South Korea; Corresponding authors.Department of Predictive Toxicology, Korea Institute of Toxicology, Daejeon 34114, South Korea; Corresponding authors.Polyhexamethylene guanidine phosphate (PHMG-p), a humidifier disinfectant, is known to cause lung toxicity, including inflammation and pulmonary fibrosis. In this study, we aimed to investigate the effect of PHMG-p on human lung tissue models (2D epithelial cells and 3D organoids) under conditions of oxidative stress and viral infection. The effect of PHMG-p was studied by evaluating the formation of stress granules (SGs), which play a pivotal role in cellular adaptation to various stress conditions. Under oxidative stress and respiratory syncytial virus (RSV) infection, exposure to PHMG-p remarkably increased eIF2α phosphorylation, which is essential for SG-related signalling, and significantly increased SG formation. Furthermore, PHMG-p induced fibrotic gene expression and caused cell death due to severe DNA damage, which was further increased under oxidative stress and RSV infection, indicating that PHMG-p induces severe lung toxicity under stress conditions. Taken together, toxicity evaluation under various stressful conditions is necessary to accurately predict potential lung toxicity of chemicals affecting the respiratory tract.http://www.sciencedirect.com/science/article/pii/S0147651321012069DNA damageeIF2αStress granulesPolyhexamethylene guanidine phosphateLung organoidsPulmonary fibrosis |
| spellingShingle | Seri Choi Sunkyung Choi Yeongsoo Choi Namjoon Cho Seung-Yeon Kim Chang Hyun Lee Han-Jin Park Won Keun Oh Kee K. Kim Eun-Mi Kim Polyhexamethylene guanidine phosphate increases stress granule formation in human 3D lung organoids under respiratory syncytial virus infection Ecotoxicology and Environmental Safety DNA damage eIF2α Stress granules Polyhexamethylene guanidine phosphate Lung organoids Pulmonary fibrosis |
| title | Polyhexamethylene guanidine phosphate increases stress granule formation in human 3D lung organoids under respiratory syncytial virus infection |
| title_full | Polyhexamethylene guanidine phosphate increases stress granule formation in human 3D lung organoids under respiratory syncytial virus infection |
| title_fullStr | Polyhexamethylene guanidine phosphate increases stress granule formation in human 3D lung organoids under respiratory syncytial virus infection |
| title_full_unstemmed | Polyhexamethylene guanidine phosphate increases stress granule formation in human 3D lung organoids under respiratory syncytial virus infection |
| title_short | Polyhexamethylene guanidine phosphate increases stress granule formation in human 3D lung organoids under respiratory syncytial virus infection |
| title_sort | polyhexamethylene guanidine phosphate increases stress granule formation in human 3d lung organoids under respiratory syncytial virus infection |
| topic | DNA damage eIF2α Stress granules Polyhexamethylene guanidine phosphate Lung organoids Pulmonary fibrosis |
| url | http://www.sciencedirect.com/science/article/pii/S0147651321012069 |
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