Arrestin domain-containing protein 1-mediated microvesicles (ARMMs) protect against cadmium-induced neurotoxicity
Exposure to environmental heavy metals such as cadmium (Cd) is often linked to neurotoxicity but the underlying mechanisms remain poorly understood. Here we show that Arrestin domain-containing protein 1 (ARRDC1)-mediated microvesicles (ARMMs)–an important class of extracellular vesicles (EVs) whose...
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| Format: | Article |
| Language: | English |
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Elsevier
2023-12-01
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| Series: | Extracellular Vesicle |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2773041723000069 |
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| author | Zunwei Chen Zhi Qiao Charlotte R. Wirth Hae-Ryung Park Quan Lu |
| author_facet | Zunwei Chen Zhi Qiao Charlotte R. Wirth Hae-Ryung Park Quan Lu |
| author_sort | Zunwei Chen |
| collection | DOAJ |
| description | Exposure to environmental heavy metals such as cadmium (Cd) is often linked to neurotoxicity but the underlying mechanisms remain poorly understood. Here we show that Arrestin domain-containing protein 1 (ARRDC1)-mediated microvesicles (ARMMs)–an important class of extracellular vesicles (EVs) whose biogenesis occurs at the plasma membrane–protect against Cd-induced neurotoxicity. Cd increased the production of EVs, including ARMMs, in a human neural progenitor cell line, ReNcell CX (ReN) cells. ReN cells that lack ARMMs production as a result of CRISPR-mediated ARRDC1 knockout were more susceptible to Cd toxicity as evidenced by increased LDH production as well as elevated level of oxidative stress markers. Importantly, adding ARMMs back to the ARRDC1-knockout ReN cells significantly reduced Cd-induced toxicity. Consistent with this finding, proteomics data showed that anti-oxidative stress proteins are enriched in ARMMs secreted from ReN cells. Together our study reveals a novel protective role of ARMMs in Cd neurotoxicity and suggests that ARMMs may be used therapeutically to reduce neurotoxicity caused by exposure to Cd and potentially other metal toxicants. |
| format | Article |
| id | doaj-art-dfbef20b59734c6f82083a76ba22fd0f |
| institution | DOAJ |
| issn | 2773-0417 |
| language | English |
| publishDate | 2023-12-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Extracellular Vesicle |
| spelling | doaj-art-dfbef20b59734c6f82083a76ba22fd0f2025-08-20T02:50:23ZengElsevierExtracellular Vesicle2773-04172023-12-01210002710.1016/j.vesic.2023.100027Arrestin domain-containing protein 1-mediated microvesicles (ARMMs) protect against cadmium-induced neurotoxicityZunwei Chen0Zhi Qiao1Charlotte R. Wirth2Hae-Ryung Park3Quan Lu4Program in Molecular and Integrative Physiological Sciences, Department of Environmental Health, Harvard T.H. Chan School of Public Health, Boston, MA, United States of AmericaProgram in Molecular and Integrative Physiological Sciences, Department of Environmental Health, Harvard T.H. Chan School of Public Health, Boston, MA, United States of AmericaProgram in Molecular and Integrative Physiological Sciences, Department of Environmental Health, Harvard T.H. Chan School of Public Health, Boston, MA, United States of AmericaDepartment of Environmental Medicine, School of Medicine and Dentistry, University of Rochester, Rochester, NY, United States of AmericaProgram in Molecular and Integrative Physiological Sciences, Department of Environmental Health, Harvard T.H. Chan School of Public Health, Boston, MA, United States of America; Correspondence to: Program in Molecular and Integrative Physiological Sciences, Department of Environmental Health, Harvard T.H. Chan School of Public Health, 665 Huntington Avenue, Boston, MA 02115, United States of AmericaExposure to environmental heavy metals such as cadmium (Cd) is often linked to neurotoxicity but the underlying mechanisms remain poorly understood. Here we show that Arrestin domain-containing protein 1 (ARRDC1)-mediated microvesicles (ARMMs)–an important class of extracellular vesicles (EVs) whose biogenesis occurs at the plasma membrane–protect against Cd-induced neurotoxicity. Cd increased the production of EVs, including ARMMs, in a human neural progenitor cell line, ReNcell CX (ReN) cells. ReN cells that lack ARMMs production as a result of CRISPR-mediated ARRDC1 knockout were more susceptible to Cd toxicity as evidenced by increased LDH production as well as elevated level of oxidative stress markers. Importantly, adding ARMMs back to the ARRDC1-knockout ReN cells significantly reduced Cd-induced toxicity. Consistent with this finding, proteomics data showed that anti-oxidative stress proteins are enriched in ARMMs secreted from ReN cells. Together our study reveals a novel protective role of ARMMs in Cd neurotoxicity and suggests that ARMMs may be used therapeutically to reduce neurotoxicity caused by exposure to Cd and potentially other metal toxicants.http://www.sciencedirect.com/science/article/pii/S2773041723000069Heavy metalsNeurotoxicityExtracellular vesiclesARRDC1Proteomics |
| spellingShingle | Zunwei Chen Zhi Qiao Charlotte R. Wirth Hae-Ryung Park Quan Lu Arrestin domain-containing protein 1-mediated microvesicles (ARMMs) protect against cadmium-induced neurotoxicity Extracellular Vesicle Heavy metals Neurotoxicity Extracellular vesicles ARRDC1 Proteomics |
| title | Arrestin domain-containing protein 1-mediated microvesicles (ARMMs) protect against cadmium-induced neurotoxicity |
| title_full | Arrestin domain-containing protein 1-mediated microvesicles (ARMMs) protect against cadmium-induced neurotoxicity |
| title_fullStr | Arrestin domain-containing protein 1-mediated microvesicles (ARMMs) protect against cadmium-induced neurotoxicity |
| title_full_unstemmed | Arrestin domain-containing protein 1-mediated microvesicles (ARMMs) protect against cadmium-induced neurotoxicity |
| title_short | Arrestin domain-containing protein 1-mediated microvesicles (ARMMs) protect against cadmium-induced neurotoxicity |
| title_sort | arrestin domain containing protein 1 mediated microvesicles armms protect against cadmium induced neurotoxicity |
| topic | Heavy metals Neurotoxicity Extracellular vesicles ARRDC1 Proteomics |
| url | http://www.sciencedirect.com/science/article/pii/S2773041723000069 |
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