PMMA nanoplastics induce gastric epithelial cellular senescence and cGAS-STING-mediated inflammation via ROS overproduction and NHEJ suppression
The increasing environmental presence of nanoplastics (NPs) has raised concerns about their potential impact on biological systems. We investigated the repercussions of polymethyl methacrylate (PMMA) NPs exposure on normal gastric epithelial cells and revealed a pronounced increase in senescence-ass...
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Elsevier
2024-11-01
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| Series: | Ecotoxicology and Environmental Safety |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S0147651324013605 |
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| author | Xiao Li Yixing Huang Dan Zu Haidong Liu Hanyi He Qimei Bao Yanhua He Chen Liang Guoyan Luo Yaoshu Teng Yin Shi Zu Ye Xiangdong Cheng |
| author_facet | Xiao Li Yixing Huang Dan Zu Haidong Liu Hanyi He Qimei Bao Yanhua He Chen Liang Guoyan Luo Yaoshu Teng Yin Shi Zu Ye Xiangdong Cheng |
| author_sort | Xiao Li |
| collection | DOAJ |
| description | The increasing environmental presence of nanoplastics (NPs) has raised concerns about their potential impact on biological systems. We investigated the repercussions of polymethyl methacrylate (PMMA) NPs exposure on normal gastric epithelial cells and revealed a pronounced increase in senescence-associated β-galactosidase activity and G1 phase cell cycle arrest. Our study demonstrated a dose-dependent increase in reactive oxygen species (ROS) and DNA damage, underscoring the pivotal role of ROS in PMMA NPs-mediated effects, a novel contribution to the existing body of knowledge dominated by polystyrene particles. Furthermore, we explored the influence of PMMA NPs on DNA damage response mechanisms, highlighting the significant inhibition of nonhomologous end-joining (NHEJ). Our findings help to elucidate the consequent genomic instability, as evidenced by increased chromosomal aberrations and micronuclei formation. By connecting these cellular manifestations to organism-level effects, we hypothesize that PMMA NPs play a critical role in aging processes. Our work revealed an activated cGAS-STING signaling pathway after PMMA NPs exposure, which correlated with aging-related inflammation and behavioral changes in mice. Importantly, our study provides comprehensive evidence of PMMA NPs-induced premature aging in gastric epithelial cells, shedding light on the molecular intricacies underlying DNA damage, repair impairment, and inflammation. Our research prompts heightened caution regarding the risks of NPs exposure and calls for further investigation into the broader implications of these environmental pollutants on aging processes in higher organisms. |
| format | Article |
| id | doaj-art-f94a922b3a004de8a9daed375fe62f00 |
| institution | Kabale University |
| issn | 0147-6513 |
| language | English |
| publishDate | 2024-11-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Ecotoxicology and Environmental Safety |
| spelling | doaj-art-f94a922b3a004de8a9daed375fe62f002024-11-21T06:02:03ZengElsevierEcotoxicology and Environmental Safety0147-65132024-11-01287117284PMMA nanoplastics induce gastric epithelial cellular senescence and cGAS-STING-mediated inflammation via ROS overproduction and NHEJ suppressionXiao Li0Yixing Huang1Dan Zu2Haidong Liu3Hanyi He4Qimei Bao5Yanhua He6Chen Liang7Guoyan Luo8Yaoshu Teng9Yin Shi10Zu Ye11Xiangdong Cheng12The Second Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou 310053, China; Zhejiang Cancer Hospital, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou 310022, China; Key Laboratory of Prevention, Diagnosis and Therapy of Upper Gastrointestinal Cancer of Zhejiang Province, Hangzhou 310022, ChinaZhejiang Cancer Hospital, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou 310022, China; Zhejiang University School of Medicine, Hangzhou 310058, China; Department of Otorhinolaryngology, Hangzhou First People's Hospital, Zhejiang University School of Medicine, Hangzhou 310006, ChinaZhejiang Cancer Hospital, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou 310022, China; Key Laboratory of Prevention, Diagnosis and Therapy of Upper Gastrointestinal Cancer of Zhejiang Province, Hangzhou 310022, China; School of Life Sciences, Tianjin University, Tianjin 300100, ChinaZhejiang Cancer Hospital, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou 310022, China; Key Laboratory of Prevention, Diagnosis and Therapy of Upper Gastrointestinal Cancer of Zhejiang Province, Hangzhou 310022, ChinaZhejiang Cancer Hospital, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou 310022, China; Key Laboratory of Prevention, Diagnosis and Therapy of Upper Gastrointestinal Cancer of Zhejiang Province, Hangzhou 310022, ChinaZhejiang Cancer Hospital, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou 310022, China; Key Laboratory of Prevention, Diagnosis and Therapy of Upper Gastrointestinal Cancer of Zhejiang Province, Hangzhou 310022, ChinaZhejiang Cancer Hospital, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou 310022, China; Key Laboratory of Prevention, Diagnosis and Therapy of Upper Gastrointestinal Cancer of Zhejiang Province, Hangzhou 310022, ChinaZhejiang Cancer Hospital, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou 310022, China; Key Laboratory of Prevention, Diagnosis and Therapy of Upper Gastrointestinal Cancer of Zhejiang Province, Hangzhou 310022, ChinaZhejiang Cancer Hospital, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou 310022, ChinaZhejiang University School of Medicine, Hangzhou 310058, China; Department of Otorhinolaryngology, Hangzhou First People's Hospital, Zhejiang University School of Medicine, Hangzhou 310006, ChinaDepartment of Biochemistry, and Department of Pulmonology Children's Hospital, Zhejiang University School of Medicine, Hangzhou 310058, China; Corresponding author.Zhejiang Cancer Hospital, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou 310022, China; Key Laboratory of Prevention, Diagnosis and Therapy of Upper Gastrointestinal Cancer of Zhejiang Province, Hangzhou 310022, China; Zhejiang Provincial Research Center for Upper Gastrointestinal Tract Cancer, Zhejiang Cancer Hospital, Hangzhou 310022, China; Corresponding authors at: Zhejiang Cancer Hospital, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou 310022, China.Zhejiang Cancer Hospital, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou 310022, China; Key Laboratory of Prevention, Diagnosis and Therapy of Upper Gastrointestinal Cancer of Zhejiang Province, Hangzhou 310022, China; Zhejiang Provincial Research Center for Upper Gastrointestinal Tract Cancer, Zhejiang Cancer Hospital, Hangzhou 310022, China; Corresponding authors at: Zhejiang Cancer Hospital, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou 310022, China.The increasing environmental presence of nanoplastics (NPs) has raised concerns about their potential impact on biological systems. We investigated the repercussions of polymethyl methacrylate (PMMA) NPs exposure on normal gastric epithelial cells and revealed a pronounced increase in senescence-associated β-galactosidase activity and G1 phase cell cycle arrest. Our study demonstrated a dose-dependent increase in reactive oxygen species (ROS) and DNA damage, underscoring the pivotal role of ROS in PMMA NPs-mediated effects, a novel contribution to the existing body of knowledge dominated by polystyrene particles. Furthermore, we explored the influence of PMMA NPs on DNA damage response mechanisms, highlighting the significant inhibition of nonhomologous end-joining (NHEJ). Our findings help to elucidate the consequent genomic instability, as evidenced by increased chromosomal aberrations and micronuclei formation. By connecting these cellular manifestations to organism-level effects, we hypothesize that PMMA NPs play a critical role in aging processes. Our work revealed an activated cGAS-STING signaling pathway after PMMA NPs exposure, which correlated with aging-related inflammation and behavioral changes in mice. Importantly, our study provides comprehensive evidence of PMMA NPs-induced premature aging in gastric epithelial cells, shedding light on the molecular intricacies underlying DNA damage, repair impairment, and inflammation. Our research prompts heightened caution regarding the risks of NPs exposure and calls for further investigation into the broader implications of these environmental pollutants on aging processes in higher organisms.http://www.sciencedirect.com/science/article/pii/S0147651324013605PMMA nanoplasticsCellular senescenceROSNHEJGenomic instability |
| spellingShingle | Xiao Li Yixing Huang Dan Zu Haidong Liu Hanyi He Qimei Bao Yanhua He Chen Liang Guoyan Luo Yaoshu Teng Yin Shi Zu Ye Xiangdong Cheng PMMA nanoplastics induce gastric epithelial cellular senescence and cGAS-STING-mediated inflammation via ROS overproduction and NHEJ suppression Ecotoxicology and Environmental Safety PMMA nanoplastics Cellular senescence ROS NHEJ Genomic instability |
| title | PMMA nanoplastics induce gastric epithelial cellular senescence and cGAS-STING-mediated inflammation via ROS overproduction and NHEJ suppression |
| title_full | PMMA nanoplastics induce gastric epithelial cellular senescence and cGAS-STING-mediated inflammation via ROS overproduction and NHEJ suppression |
| title_fullStr | PMMA nanoplastics induce gastric epithelial cellular senescence and cGAS-STING-mediated inflammation via ROS overproduction and NHEJ suppression |
| title_full_unstemmed | PMMA nanoplastics induce gastric epithelial cellular senescence and cGAS-STING-mediated inflammation via ROS overproduction and NHEJ suppression |
| title_short | PMMA nanoplastics induce gastric epithelial cellular senescence and cGAS-STING-mediated inflammation via ROS overproduction and NHEJ suppression |
| title_sort | pmma nanoplastics induce gastric epithelial cellular senescence and cgas sting mediated inflammation via ros overproduction and nhej suppression |
| topic | PMMA nanoplastics Cellular senescence ROS NHEJ Genomic instability |
| url | http://www.sciencedirect.com/science/article/pii/S0147651324013605 |
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