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Treatment of polyethylene microplastics degraded by ultraviolet light irradiation causes lysosome-deregulated cell death

Background Microplastics (MPs), plastic particles 

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Published in:Scientific reports 2024-10, Vol.14 (1), p.24008-11, Article 24008
Main Authors: Manabe, Sota, Haga, Yuya, Tsujino, Hirofumi, Ikuno, Yudai, Asahara, Haruyasu, Higashisaka, Kazuma, Tsutsumi, Yasuo
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creator Manabe, Sota
Haga, Yuya
Tsujino, Hirofumi
Ikuno, Yudai
Asahara, Haruyasu
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Tsutsumi, Yasuo
description Background Microplastics (MPs), plastic particles 
doi_str_mv 10.1038/s41598-024-74800-y
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To assess the potential risk of MPs on human health, it is essential to consider the physicochemical properties of environmental MPs, including polymer types, size, shape, and surface chemical modifications. Notably, environmental MPs undergo degradation due to external factors such as ultraviolet (UV) rays and waves, leading to changes in their surface characteristics. However, limited knowledge exists regarding the health effects of MPs, with a specific focus on their surface degradation. This study concentrates on cytotoxic MPs with surface degradation through UV irradiation, aiming to identify the mechanisms underlying their cell toxicity. Results Polyethylene (PE) and surface-degraded PE achieved through UV light irradiation were employed as model MPs in this study. We explored the impact of PE and degraded PE on cell death in murine macrophage cell line RAW264.7 cells and human monocyte cell line THP-1 cells. Flow cytometric analysis revealed that degraded PE induced programmed cell death without activating caspase 3, while non-degraded PE did not trigger programmed cell death. These findings suggest that degraded PE might induce programmed cell death through mechanisms other than caspase-driven apoptosis. To understand the mechanisms of cell death, we investigated how cells responded to degraded PE-induced cellular stress. Immunofluorescence and western blotting analyses demonstrated that degraded PE induced autophagosome formation and increased p62 expression, indicating inhibited autophagy flux after exposure to degraded PE. Furthermore, degraded PE exposure led to a decrease in acidic lysosomes, indicating lysosomal dysregulation. These results imply that degraded PE induces lysosomal dysfunction, subsequently causing autophagy dysregulation and cell death. Conclusions This study unveils that UV-induced degradation of PE results in cell death attributed to lysosomal dysfunction. The findings presented herein provide novel insights into the effects of surface-degraded MPs on biological responses.</description><identifier>ISSN: 2045-2322</identifier><identifier>EISSN: 2045-2322</identifier><identifier>DOI: 10.1038/s41598-024-74800-y</identifier><identifier>PMID: 39402130</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>631/80/82 ; 704/172/4081 ; Animals ; Apoptosis ; Apoptosis - drug effects ; Apoptosis - radiation effects ; Autophagy ; Autophagy - drug effects ; Autophagy - radiation effects ; Biodegradation ; Caspase-3 ; Cell death ; Cell Death - drug effects ; Cell Death - radiation effects ; Cell size ; Cellular stress response ; Cytotoxicity ; Environmental degradation ; Flow cytometry ; Humanities and Social Sciences ; Humans ; Immunofluorescence ; Irradiation ; Lysosome dysregulation ; Lysosomes ; Lysosomes - drug effects ; Lysosomes - metabolism ; Macrophages ; Mice ; Microplastics ; Microplastics - toxicity ; Monocytes ; Mortality ; multidisciplinary ; Physicochemical properties ; Plastic pollution ; Polyethylene ; Polyethylene microplastics ; Polymers ; RAW 264.7 Cells ; Science ; Science (multidisciplinary) ; Surface degradation of microplastics ; THP-1 Cells ; Ultraviolet radiation ; Ultraviolet Rays - adverse effects ; Western blotting</subject><ispartof>Scientific reports, 2024-10, Vol.14 (1), p.24008-11, Article 24008</ispartof><rights>The Author(s) 2024</rights><rights>2024. The Author(s).</rights><rights>The Author(s) 2024. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>The Author(s) 2024 2024</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c466t-2ee4afd267cf16e30756da1a3229d73129fd6d401d7936970fa421586c2575b13</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.proquest.com/docview/3116458568/fulltextPDF?pq-origsite=primo$$EPDF$$P50$$Gproquest$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.proquest.com/docview/3116458568?pq-origsite=primo$$EHTML$$P50$$Gproquest$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,885,25753,27924,27925,37012,37013,44590,53791,53793,75126</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/39402130$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Manabe, Sota</creatorcontrib><creatorcontrib>Haga, Yuya</creatorcontrib><creatorcontrib>Tsujino, Hirofumi</creatorcontrib><creatorcontrib>Ikuno, Yudai</creatorcontrib><creatorcontrib>Asahara, Haruyasu</creatorcontrib><creatorcontrib>Higashisaka, Kazuma</creatorcontrib><creatorcontrib>Tsutsumi, Yasuo</creatorcontrib><title>Treatment of polyethylene microplastics degraded by ultraviolet light irradiation causes lysosome-deregulated cell death</title><title>Scientific reports</title><addtitle>Sci Rep</addtitle><addtitle>Sci Rep</addtitle><description>Background Microplastics (MPs), plastic particles &lt; 5 mm in size, are prevalent in the environment, and human exposure to them is inevitable. To assess the potential risk of MPs on human health, it is essential to consider the physicochemical properties of environmental MPs, including polymer types, size, shape, and surface chemical modifications. Notably, environmental MPs undergo degradation due to external factors such as ultraviolet (UV) rays and waves, leading to changes in their surface characteristics. However, limited knowledge exists regarding the health effects of MPs, with a specific focus on their surface degradation. This study concentrates on cytotoxic MPs with surface degradation through UV irradiation, aiming to identify the mechanisms underlying their cell toxicity. Results Polyethylene (PE) and surface-degraded PE achieved through UV light irradiation were employed as model MPs in this study. We explored the impact of PE and degraded PE on cell death in murine macrophage cell line RAW264.7 cells and human monocyte cell line THP-1 cells. Flow cytometric analysis revealed that degraded PE induced programmed cell death without activating caspase 3, while non-degraded PE did not trigger programmed cell death. These findings suggest that degraded PE might induce programmed cell death through mechanisms other than caspase-driven apoptosis. To understand the mechanisms of cell death, we investigated how cells responded to degraded PE-induced cellular stress. Immunofluorescence and western blotting analyses demonstrated that degraded PE induced autophagosome formation and increased p62 expression, indicating inhibited autophagy flux after exposure to degraded PE. Furthermore, degraded PE exposure led to a decrease in acidic lysosomes, indicating lysosomal dysregulation. These results imply that degraded PE induces lysosomal dysfunction, subsequently causing autophagy dysregulation and cell death. Conclusions This study unveils that UV-induced degradation of PE results in cell death attributed to lysosomal dysfunction. The findings presented herein provide novel insights into the effects of surface-degraded MPs on biological responses.</description><subject>631/80/82</subject><subject>704/172/4081</subject><subject>Animals</subject><subject>Apoptosis</subject><subject>Apoptosis - drug effects</subject><subject>Apoptosis - radiation effects</subject><subject>Autophagy</subject><subject>Autophagy - drug effects</subject><subject>Autophagy - radiation effects</subject><subject>Biodegradation</subject><subject>Caspase-3</subject><subject>Cell death</subject><subject>Cell Death - drug effects</subject><subject>Cell Death - radiation effects</subject><subject>Cell size</subject><subject>Cellular stress response</subject><subject>Cytotoxicity</subject><subject>Environmental degradation</subject><subject>Flow cytometry</subject><subject>Humanities and Social Sciences</subject><subject>Humans</subject><subject>Immunofluorescence</subject><subject>Irradiation</subject><subject>Lysosome dysregulation</subject><subject>Lysosomes</subject><subject>Lysosomes - drug effects</subject><subject>Lysosomes - metabolism</subject><subject>Macrophages</subject><subject>Mice</subject><subject>Microplastics</subject><subject>Microplastics - toxicity</subject><subject>Monocytes</subject><subject>Mortality</subject><subject>multidisciplinary</subject><subject>Physicochemical properties</subject><subject>Plastic pollution</subject><subject>Polyethylene</subject><subject>Polyethylene microplastics</subject><subject>Polymers</subject><subject>RAW 264.7 Cells</subject><subject>Science</subject><subject>Science (multidisciplinary)</subject><subject>Surface degradation of microplastics</subject><subject>THP-1 Cells</subject><subject>Ultraviolet radiation</subject><subject>Ultraviolet Rays - adverse effects</subject><subject>Western blotting</subject><issn>2045-2322</issn><issn>2045-2322</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2024</creationdate><recordtype>article</recordtype><sourceid>PIMPY</sourceid><sourceid>DOA</sourceid><recordid>eNp9kk1v1DAQhiMEolXpH-CAInHhEvC3kxNCFR-VKnEpZ2vWnmSzcuLFdiry7_HultJywBdbnncez4zfqnpNyXtKePshCSq7tiFMNFq0hDTrs-qcESEbxhl7_uh8Vl2mtCNlSdYJ2r2szngnCKOcnFe_biNCnnDOdejrffAr5u3qccZ6Gm0Mew8pjzbVDocIDl29WevF5wh3Y_CYaz8O21yPsQRHyGOYawtLwlT7NYUUJmwcRhwWD7kkW_S-oCBvX1UvevAJL-_3i-rHl8-3V9-am-9fr68-3TRWKJUbhiigd0xp21OFnGipHFAofXVOc8q63iknCHW646rTpAfBqGyVZVLLDeUX1fWJ6wLszD6OE8TVBBjN8SLEwUAsHXo0knOutJNcKSqUhRYk05QSIixIq2VhfTyx9stmQmfL1CL4J9CnkXncmiHcGUqF5i0_VPPunhDDzwVTNtOYDkOBGcOSDKdUKa1azYr07T_SXVjiXGZ1VAnZStUWFTupyl-lFLF_qIYSczCKORnFFKOYo1HMWpLePO7jIeWPLYqAnwSphOYB49-3_4P9DZWrysY</recordid><startdate>20241014</startdate><enddate>20241014</enddate><creator>Manabe, Sota</creator><creator>Haga, Yuya</creator><creator>Tsujino, Hirofumi</creator><creator>Ikuno, Yudai</creator><creator>Asahara, Haruyasu</creator><creator>Higashisaka, Kazuma</creator><creator>Tsutsumi, Yasuo</creator><general>Nature Publishing Group UK</general><general>Nature Publishing Group</general><general>Nature Portfolio</general><scope>C6C</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7X7</scope><scope>7XB</scope><scope>88A</scope><scope>88E</scope><scope>88I</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M2P</scope><scope>M7P</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>Q9U</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope></search><sort><creationdate>20241014</creationdate><title>Treatment of polyethylene microplastics degraded by ultraviolet light irradiation causes lysosome-deregulated cell death</title><author>Manabe, Sota ; 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To assess the potential risk of MPs on human health, it is essential to consider the physicochemical properties of environmental MPs, including polymer types, size, shape, and surface chemical modifications. Notably, environmental MPs undergo degradation due to external factors such as ultraviolet (UV) rays and waves, leading to changes in their surface characteristics. However, limited knowledge exists regarding the health effects of MPs, with a specific focus on their surface degradation. This study concentrates on cytotoxic MPs with surface degradation through UV irradiation, aiming to identify the mechanisms underlying their cell toxicity. Results Polyethylene (PE) and surface-degraded PE achieved through UV light irradiation were employed as model MPs in this study. We explored the impact of PE and degraded PE on cell death in murine macrophage cell line RAW264.7 cells and human monocyte cell line THP-1 cells. Flow cytometric analysis revealed that degraded PE induced programmed cell death without activating caspase 3, while non-degraded PE did not trigger programmed cell death. These findings suggest that degraded PE might induce programmed cell death through mechanisms other than caspase-driven apoptosis. To understand the mechanisms of cell death, we investigated how cells responded to degraded PE-induced cellular stress. Immunofluorescence and western blotting analyses demonstrated that degraded PE induced autophagosome formation and increased p62 expression, indicating inhibited autophagy flux after exposure to degraded PE. Furthermore, degraded PE exposure led to a decrease in acidic lysosomes, indicating lysosomal dysregulation. These results imply that degraded PE induces lysosomal dysfunction, subsequently causing autophagy dysregulation and cell death. Conclusions This study unveils that UV-induced degradation of PE results in cell death attributed to lysosomal dysfunction. The findings presented herein provide novel insights into the effects of surface-degraded MPs on biological responses.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>39402130</pmid><doi>10.1038/s41598-024-74800-y</doi><tpages>11</tpages><oa>free_for_read</oa></addata></record>
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subjects 631/80/82
704/172/4081
Animals
Apoptosis
Apoptosis - drug effects
Apoptosis - radiation effects
Autophagy
Autophagy - drug effects
Autophagy - radiation effects
Biodegradation
Caspase-3
Cell death
Cell Death - drug effects
Cell Death - radiation effects
Cell size
Cellular stress response
Cytotoxicity
Environmental degradation
Flow cytometry
Humanities and Social Sciences
Humans
Immunofluorescence
Irradiation
Lysosome dysregulation
Lysosomes
Lysosomes - drug effects
Lysosomes - metabolism
Macrophages
Mice
Microplastics
Microplastics - toxicity
Monocytes
Mortality
multidisciplinary
Physicochemical properties
Plastic pollution
Polyethylene
Polyethylene microplastics
Polymers
RAW 264.7 Cells
Science
Science (multidisciplinary)
Surface degradation of microplastics
THP-1 Cells
Ultraviolet radiation
Ultraviolet Rays - adverse effects
Western blotting
title Treatment of polyethylene microplastics degraded by ultraviolet light irradiation causes lysosome-deregulated cell death
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