Environment & Health最新文献

{"title":"Independent and Combined Associations between Metals Exposure and Inflammatory Markers among the General U.S. Adults.","authors":"Xinrui Feng, Yaoyu Luo, Min Zheng, Xiaojie Sun, Xiantao Shen","doi":"10.1021/envhealth.4c00097","DOIUrl":"10.1021/envhealth.4c00097","url":null,"abstract":"<p><p>Exposure to metals can trigger a series of diseases by dysregulating the human immune system, but there is still a lack of systematic studies assessing the independent and combined effects of exposure to metals on immune function in the general population, particularly concerning inflammation markers. This cross-sectional study was designed to mainly examine the associations between urinary metal mixtures and inflammatory markers, including white blood cell (WBC), platelet count (PLT), mean platelet volume (MPV), MPV/PLT ratio (MPR), platelet-to-lymphocyte ratio (PLR), and neutrophil-to-lymphocyte ratio (NLR). A total of 3451 participants aged ≥20 years were selected from the 2013-2016 National Health and Nutrition Examination Survey. Generalized linear models were used to investigate the relationships of exposure to single metals on inflammatory markers. Associations between coexposure to multiple metals and inflammatory markers were determined using weighted quantile sum regression and quantile g-computation. Barium, cadmium, lead, thallium, and cobalt showed significant associations with MPV, PLR, and NLR. Metal mixtures showed a negative association with MPV, while they had positive associations with PLR and NLR. Overall, our study highlights the significant effects of multiple metals exposure on inflammation markers, including MPV, PLR, and NLR, among U.S. adults. Thereinto, uranium, cadmium, and cobalt were identified as major contributors. Further prospective studies representative of other countries are warranted to either validate or refute our findings.</p>","PeriodicalId":29795,"journal":{"name":"Environment & Health","volume":"3 3","pages":"282-290"},"PeriodicalIF":0.0,"publicationDate":"2024-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11934204/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143721667","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Gestational Exposure to Endocrine-Disrupting Chemicals of Emerging Concern and the Risk of Developing Gestational Diabetes Mellitus: A Comprehensive Investigation of Sex-Specific and Trimester-Specific Associations","authors":"Jinfeng Fu,&nbsp;Yao Yao,&nbsp;Zhihong Huang,&nbsp;Zhihui Guo,&nbsp;Xinxin Tang,&nbsp;Xulong Chen,&nbsp;Xinjie Li,&nbsp;Yiming Ge,&nbsp;Bingjun Lu,&nbsp;Yujie Sha and Shaoyou Lu*,&nbsp;","doi":"10.1021/envhealth.4c0020210.1021/envhealth.4c00202","DOIUrl":"https://doi.org/10.1021/envhealth.4c00202https://doi.org/10.1021/envhealth.4c00202","url":null,"abstract":"<p >Gestational diabetes mellitus (GDM) is a type of diabetes that arises during pregnancy, leading to long-term adverse consequences for maternal health and fetal development. However, the specific role of endocrine-disrupting chemicals (EDCs) in the pathogenesis of GDM remains controversial. This prospective cohort study sought to investigate how coexposure to bisphenols, parabens, triclosan (TCS), benzophenone-type UV filters, and neonicotinoids (NEOs) affects the odds of GDM. Quantile-based g-computation and Bayesian kernel machine regression showed a significant inverse relationship between EDC mixtures and the reduced risk of GDM (OR = 0.34, 95% CI: 0.13–0.87), which was mainly explained by bisphenol (OR = 0.49, 95% CI: 0.29–0.80) and paraben (OR = 0.60, 95% CI: 0.40–0.91) exposure. Bisphenol S (BPS), bisphenol Z (BPZ), ethylparaben (EtP), propylparaben (PrP), and butylparaben (BuP) were identified as key contributors to the joint effect. In addition, subgroup analyses suggested that the bisphenols-GDM association was more pronounced in younger/normal-weight participants. The sex-specific impact of exposure to bisphenols on the development of GDM was observed, whereas the second trimester represented a critical window for EDC exposure. Continued research efforts, focusing on causal pathways and nonmonotonic relationships, will be crucial to elucidate the complex influence of EDC exposure on the development of GDM.</p>","PeriodicalId":29795,"journal":{"name":"Environment & Health","volume":"3 3","pages":"271–281 271–281"},"PeriodicalIF":0.0,"publicationDate":"2024-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/epdf/10.1021/envhealth.4c00202","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143667138","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Independent and Combined Associations between Metals Exposure and Inflammatory Markers among the General U.S. Adults","authors":"Xinrui Feng,&nbsp;Yaoyu Luo,&nbsp;Min Zheng,&nbsp;Xiaojie Sun* and Xiantao Shen*,&nbsp;","doi":"10.1021/envhealth.4c0009710.1021/envhealth.4c00097","DOIUrl":"https://doi.org/10.1021/envhealth.4c00097https://doi.org/10.1021/envhealth.4c00097","url":null,"abstract":"<p >Exposure to metals can trigger a series of diseases by dysregulating the human immune system, but there is still a lack of systematic studies assessing the independent and combined effects of exposure to metals on immune function in the general population, particularly concerning inflammation markers. This cross-sectional study was designed to mainly examine the associations between urinary metal mixtures and inflammatory markers, including white blood cell (WBC), platelet count (PLT), mean platelet volume (MPV), MPV/PLT ratio (MPR), platelet-to-lymphocyte ratio (PLR), and neutrophil-to-lymphocyte ratio (NLR). A total of 3451 participants aged ≥20 years were selected from the 2013–2016 National Health and Nutrition Examination Survey. Generalized linear models were used to investigate the relationships of exposure to single metals on inflammatory markers. Associations between coexposure to multiple metals and inflammatory markers were determined using weighted quantile sum regression and quantile g-computation. Barium, cadmium, lead, thallium, and cobalt showed significant associations with MPV, PLR, and NLR. Metal mixtures showed a negative association with MPV, while they had positive associations with PLR and NLR. Overall, our study highlights the significant effects of multiple metals exposure on inflammation markers, including MPV, PLR, and NLR, among U.S. adults. Thereinto, uranium, cadmium, and cobalt were identified as major contributors. Further prospective studies representative of other countries are warranted to either validate or refute our findings.</p>","PeriodicalId":29795,"journal":{"name":"Environment & Health","volume":"3 3","pages":"282–290 282–290"},"PeriodicalIF":0.0,"publicationDate":"2024-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/epdf/10.1021/envhealth.4c00097","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143667139","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Gestational Exposure to Endocrine-Disrupting Chemicals of Emerging Concern and the Risk of Developing Gestational Diabetes Mellitus: A Comprehensive Investigation of Sex-Specific and Trimester-Specific Associations.","authors":"Jinfeng Fu, Yao Yao, Zhihong Huang, Zhihui Guo, Xinxin Tang, Xulong Chen, Xinjie Li, Yiming Ge, Bingjun Lu, Yujie Sha, Shaoyou Lu","doi":"10.1021/envhealth.4c00202","DOIUrl":"10.1021/envhealth.4c00202","url":null,"abstract":"<p><p>Gestational diabetes mellitus (GDM) is a type of diabetes that arises during pregnancy, leading to long-term adverse consequences for maternal health and fetal development. However, the specific role of endocrine-disrupting chemicals (EDCs) in the pathogenesis of GDM remains controversial. This prospective cohort study sought to investigate how coexposure to bisphenols, parabens, triclosan (TCS), benzophenone-type UV filters, and neonicotinoids (NEOs) affects the odds of GDM. Quantile-based g-computation and Bayesian kernel machine regression showed a significant inverse relationship between EDC mixtures and the reduced risk of GDM (OR = 0.34, 95% CI: 0.13-0.87), which was mainly explained by bisphenol (OR = 0.49, 95% CI: 0.29-0.80) and paraben (OR = 0.60, 95% CI: 0.40-0.91) exposure. Bisphenol S (BPS), bisphenol Z (BPZ), ethylparaben (EtP), propylparaben (PrP), and butylparaben (BuP) were identified as key contributors to the joint effect. In addition, subgroup analyses suggested that the bisphenols-GDM association was more pronounced in younger/normal-weight participants. The sex-specific impact of exposure to bisphenols on the development of GDM was observed, whereas the second trimester represented a critical window for EDC exposure. Continued research efforts, focusing on causal pathways and nonmonotonic relationships, will be crucial to elucidate the complex influence of EDC exposure on the development of GDM.</p>","PeriodicalId":29795,"journal":{"name":"Environment & Health","volume":"3 3","pages":"271-281"},"PeriodicalIF":0.0,"publicationDate":"2024-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11934205/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143721664","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Environmental Enrichment Exposure Alleviates Geriatric Depressive-Like Symptoms through Regulating Neurogenesis and Neuroinflammation.","authors":"Wei Zhang, Guangyu Jiang, Huiwen Kang, Jingyu Wang, Ziyan Liu, Ziyan Wang, Danyang Huang, Ai Gao","doi":"10.1021/envhealth.4c00186","DOIUrl":"10.1021/envhealth.4c00186","url":null,"abstract":"<p><p>Environmental enrichment (EE) is a significant approach to influencing brain function by altering the environment and changing living conditions and has been shown to modulate mood-related diseases, including depression. Among the elderly, depression is particularly prevalent and is often linked to social isolation. However, the specific role of EE in social isolation-related geriatric depression remains imprecise. This study was intended to explore the status of EE exposure in geriatric depression and to uncover its underlying mechanisms. We utilized 19-month-old male C57BL/6J mice, which are equivalent to humans aged 50-60 years, and induced depression through social isolation. After 2 weeks of social isolation, mice were identified as depressive by using the sugar preference test and then classified into either standard or enrichment environment groups for 4 weeks. Subsequently, conventional indices associated with depression, including neurogenesis, neurotrophic factors, and neuroinflammation, were measured. Results display that EE alleviated the depressive-like symptoms in elderly mice and enriched their social activities. Concurrently, EE regulated levels of certain neurotransmitters in the hippocampus, including the systems of glutamate, tyrosine, and histamine. Moreover, the ability of neurogenesis also increased in the hippocampus of EE mice. At the neuroinflammation level, the activation of Natural Killer (NK) cells and ARG1⁺ microglia is considered a major contributor to mediating the effects of EE-regulated geriatric depression. Collectively, these results underline the importance of EE in the treatment of geriatric depression and partially elucidate its underlying mechanism, offering valuable suggestions for treating social isolation--related depression via environmental modulation.</p>","PeriodicalId":29795,"journal":{"name":"Environment & Health","volume":"3 3","pages":"259-270"},"PeriodicalIF":0.0,"publicationDate":"2024-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11934201/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143721663","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Environmental Enrichment Exposure Alleviates Geriatric Depressive-Like Symptoms through Regulating Neurogenesis and Neuroinflammation","authors":"Wei Zhang,&nbsp;Guangyu Jiang,&nbsp;Huiwen Kang,&nbsp;Jingyu Wang,&nbsp;Ziyan Liu,&nbsp;Ziyan Wang,&nbsp;Danyang Huang and Ai Gao*,&nbsp;","doi":"10.1021/envhealth.4c0018610.1021/envhealth.4c00186","DOIUrl":"https://doi.org/10.1021/envhealth.4c00186https://doi.org/10.1021/envhealth.4c00186","url":null,"abstract":"<p >Environmental enrichment (EE) is a significant approach to influencing brain function by altering the environment and changing living conditions and has been shown to modulate mood-related diseases, including depression. Among the elderly, depression is particularly prevalent and is often linked to social isolation. However, the specific role of EE in social isolation-related geriatric depression remains imprecise. This study was intended to explore the status of EE exposure in geriatric depression and to uncover its underlying mechanisms. We utilized 19-month-old male C57BL/6J mice, which are equivalent to humans aged 50–60 years, and induced depression through social isolation. After 2 weeks of social isolation, mice were identified as depressive by using the sugar preference test and then classified into either standard or enrichment environment groups for 4 weeks. Subsequently, conventional indices associated with depression, including neurogenesis, neurotrophic factors, and neuroinflammation, were measured. Results display that EE alleviated the depressive-like symptoms in elderly mice and enriched their social activities. Concurrently, EE regulated levels of certain neurotransmitters in the hippocampus, including the systems of glutamate, tyrosine, and histamine. Moreover, the ability of neurogenesis also increased in the hippocampus of EE mice. At the neuroinflammation level, the activation of Natural Killer (NK) cells and ARG1⁺ microglia is considered a major contributor to mediating the effects of EE-regulated geriatric depression. Collectively, these results underline the importance of EE in the treatment of geriatric depression and partially elucidate its underlying mechanism, offering valuable suggestions for treating social isolation--related depression via environmental modulation.</p>","PeriodicalId":29795,"journal":{"name":"Environment & Health","volume":"3 3","pages":"259–270 259–270"},"PeriodicalIF":0.0,"publicationDate":"2024-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/epdf/10.1021/envhealth.4c00186","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143667137","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Protein Biomarkers of DNA Damage in Yeast Cells for Genotoxicity Screening","authors":"Yushi Jin,&nbsp;Boyuan Xue and Xiaohong Zhou*,&nbsp;","doi":"10.1021/envhealth.4c0016010.1021/envhealth.4c00160","DOIUrl":"https://doi.org/10.1021/envhealth.4c00160https://doi.org/10.1021/envhealth.4c00160","url":null,"abstract":"<p >Providing an unbiased and comprehensive view of the DNA damage response in cells is critical in genotoxicity screening to identify substances that cause diverse types of DNA damage. Considering that <i>S. cerevisiae</i> is one of the most well-characterized model organisms in molecular and cellular biology, we created a map of the DNA damage response network containing the reported signaling pathways in yeast cells programmed to constitutively respond to DNA damage. A collection of GFP-fused <i>S. cerevisiae</i> yeast strains treated with typical genotoxic agents illuminated the cellular response to DNA damage, thereby identifying 15 protein biomarkers encompassing all eight documented DNA damage response pathways. Three statistical and one deep learning models were proposed to interpret the quantitative molecular toxicity end point, i.e. protein effect level index (PELI), by introducing weights of 15 biomarkers in genotoxicity assessment. The method based on standard deviation exhibited the best performance, with an <i>R</i>² of 0.916 compared to the SOS/umu test and an <i>R</i>² of 0.989 compared to the comet assay. The GFP-fused yeast-based proteomic assay has minute-level resolution of pathway activation data. It provides a concise alternative for fast, efficient, and mechanistic genotoxicity screening for various environmental and health applications.</p>","PeriodicalId":29795,"journal":{"name":"Environment & Health","volume":"3 3","pages":"250–258 250–258"},"PeriodicalIF":0.0,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/epdf/10.1021/envhealth.4c00160","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143667136","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Protein Biomarkers of DNA Damage in Yeast Cells for Genotoxicity Screening.","authors":"Yushi Jin, Boyuan Xue, Xiaohong Zhou","doi":"10.1021/envhealth.4c00160","DOIUrl":"10.1021/envhealth.4c00160","url":null,"abstract":"<p><p>Providing an unbiased and comprehensive view of the DNA damage response in cells is critical in genotoxicity screening to identify substances that cause diverse types of DNA damage. Considering that <i>S. cerevisiae</i> is one of the most well-characterized model organisms in molecular and cellular biology, we created a map of the DNA damage response network containing the reported signaling pathways in yeast cells programmed to constitutively respond to DNA damage. A collection of GFP-fused <i>S. cerevisiae</i> yeast strains treated with typical genotoxic agents illuminated the cellular response to DNA damage, thereby identifying 15 protein biomarkers encompassing all eight documented DNA damage response pathways. Three statistical and one deep learning models were proposed to interpret the quantitative molecular toxicity end point, i.e. protein effect level index (PELI), by introducing weights of 15 biomarkers in genotoxicity assessment. The method based on standard deviation exhibited the best performance, with an <i>R</i> ² of 0.916 compared to the SOS/umu test and an <i>R</i> ² of 0.989 compared to the comet assay. The GFP-fused yeast-based proteomic assay has minute-level resolution of pathway activation data. It provides a concise alternative for fast, efficient, and mechanistic genotoxicity screening for various environmental and health applications.</p>","PeriodicalId":29795,"journal":{"name":"Environment & Health","volume":"3 3","pages":"250-258"},"PeriodicalIF":0.0,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11934195/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143721671","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Disruption of Copper Redox Balance and Dysfunction under <i>In Vivo</i> and <i>In Vitro</i> Alzheimer's Disease Models.","authors":"Yiteng Xia, Karl W K Tsim, Wen-Xiong Wang","doi":"10.1021/envhealth.4c00175","DOIUrl":"10.1021/envhealth.4c00175","url":null,"abstract":"<p><p>Alzheimer's disease (AD) is a neurodegenerative disorder disease mainly caused by extracellular senile plaques (SP) formed by β-amyloid (Aβ1-42) protein deposits. Copper (Cu) is an essential metal involved in neural system, and its homeostasis is the key to maintain its proper function. Herein, the subcellular locations of Cu(I) and Cu(II) in human neurodegenerative disease SH-SY5Y cells and AD mouse brains were imaged. We found that the content of Cu(II) decreased while that of Cu(I) increased under Aβ exposure, which were further verified in the brain tissues of the AD mouse model, strongly suggesting the disruption of Cu homeostasis under Aβ exposure or AD. Remarkably, the mitochondrial and lysosomal Cu(II) decreased significantly, whereas Cu(I) decreased in mitochondria but increased in lysosome. Lysosomes digested the damaged mitochondria via mitophagy to remove excess Cu(I) and maintain Cu homeostasis. The Aβ induced Cu(I) in mitochondria resulted in an overformation of reactive oxygen species and altered the morphology of this organelle. Due to the oxidative stress, glutathione (GSH) was converted into glutathione disulfide (GSSG), and Cu(I) bound with GSH was further released into the cytoplasm and absorbed by the lysosome. Transcriptomic analysis showed that genes (ATP7A/B) related to Cu transportation were upregulated, whereas genes related to mitochondrial complex were down-regulated, representing the damage of this organelle. This study demonstrated that Aβ exposure caused the disruption of intracellular homeostasis by reducing Cu(II) to Cu(I) and damaging the mitochondria, which further triggered detoxification by the lysosome. Our finding provided new insights in Aβ and AD induced Cu redox transformation and toxicity.</p>","PeriodicalId":29795,"journal":{"name":"Environment & Health","volume":"3 3","pages":"238-249"},"PeriodicalIF":0.0,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11934196/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143721641","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Disruption of Copper Redox Balance and Dysfunction under In Vivo and In Vitro Alzheimer’s Disease Models","authors":"Yiteng Xia,&nbsp;Karl W. K. Tsim and Wen-Xiong Wang*,&nbsp;","doi":"10.1021/envhealth.4c0017510.1021/envhealth.4c00175","DOIUrl":"https://doi.org/10.1021/envhealth.4c00175https://doi.org/10.1021/envhealth.4c00175","url":null,"abstract":"<p >Alzheimer’s disease (AD) is a neurodegenerative disorder disease mainly caused by extracellular senile plaques (SP) formed by β-amyloid (Aβ1–42) protein deposits. Copper (Cu) is an essential metal involved in neural system, and its homeostasis is the key to maintain its proper function. Herein, the subcellular locations of Cu(I) and Cu(II) in human neurodegenerative disease SH-SY5Y cells and AD mouse brains were imaged. We found that the content of Cu(II) decreased while that of Cu(I) increased under Aβ exposure, which were further verified in the brain tissues of the AD mouse model, strongly suggesting the disruption of Cu homeostasis under Aβ exposure or AD. Remarkably, the mitochondrial and lysosomal Cu(II) decreased significantly, whereas Cu(I) decreased in mitochondria but increased in lysosome. Lysosomes digested the damaged mitochondria via mitophagy to remove excess Cu(I) and maintain Cu homeostasis. The Aβ induced Cu(I) in mitochondria resulted in an overformation of reactive oxygen species and altered the morphology of this organelle. Due to the oxidative stress, glutathione (GSH) was converted into glutathione disulfide (GSSG), and Cu(I) bound with GSH was further released into the cytoplasm and absorbed by the lysosome. Transcriptomic analysis showed that genes (ATP7A/B) related to Cu transportation were upregulated, whereas genes related to mitochondrial complex were down-regulated, representing the damage of this organelle. This study demonstrated that Aβ exposure caused the disruption of intracellular homeostasis by reducing Cu(II) to Cu(I) and damaging the mitochondria, which further triggered detoxification by the lysosome. Our finding provided new insights in Aβ and AD induced Cu redox transformation and toxicity.</p>","PeriodicalId":29795,"journal":{"name":"Environment & Health","volume":"3 3","pages":"238–249 238–249"},"PeriodicalIF":0.0,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/epdf/10.1021/envhealth.4c00175","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143667025","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}