N-acetylcysteine attenuates PM2.5-induced apoptosis by ROS-mediated Nrf2 pathway in human embryonic stem cells
While the effects of fine particulate matter (PM2.5) on embryonic toxicity are widely accepted, its exact mechanisms have not yet been fully elucidated, which partially attribute to lack of ideal research model. Embryonic stem cells (ESCs) have the capacity to differentiate into all cell types of th...
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Veröffentlicht in: | The Science of the total environment 2019-05, Vol.666, p.713-720 |
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description | While the effects of fine particulate matter (PM2.5) on embryonic toxicity are widely accepted, its exact mechanisms have not yet been fully elucidated, which partially attribute to lack of ideal research model. Embryonic stem cells (ESCs) have the capacity to differentiate into all cell types of three germ layers. Thus, they are ideal resources for the reproductive toxicity assessment in vitro. In the present study, we investigated the effects of PM2.5 exposure on the oxidative stress and apoptosis of human ESCs (hESCs) and its possible mechanism. Our results showed that strong cytotoxicity high reactive oxygen species (ROS) level and fragmentation of nuclei were observed in the PM2.5-treated hESCs. Meanwhile, up-regulation of apoptosis as well as down-regulation of Nrf2 signaling pathway were also observed after PM2.5 treatment. However, we did not detect significant expression change or phosphorylation of Akt and Erk in PM2.5-treated hESCs. Interestingly, scavenging of PM2.5-induced ROS by N-acetylcysteine (NAC) could block cell apoptosis and rescue the activity of Nrf2 signaling pathway. In conclusion, we demonstrate that PM2.5 is toxic to hESCs by inhibition of ROS-mediated Nrf2 pathway activity. Our findings suggest activation of Nrf2 pathway will help develop new strategies for the prevention and treatment of PM2.5-associated disease.
[Display omitted]
•PM2.5 caused severe cytotoxic effects on hESCs by elevating ROS level.•PM2.5 induced down-regulation of Nrf2 signaling pathway in hESCs.•Akt and Erk pathways were not changed in PM2.5-treated hESCs.•NAC could block cell apoptosis and rescue the activity of Nrf2 signaling pathway. |
doi_str_mv | 10.1016/j.scitotenv.2019.02.307 |
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[Display omitted]
•PM2.5 caused severe cytotoxic effects on hESCs by elevating ROS level.•PM2.5 induced down-regulation of Nrf2 signaling pathway in hESCs.•Akt and Erk pathways were not changed in PM2.5-treated hESCs.•NAC could block cell apoptosis and rescue the activity of Nrf2 signaling pathway.</description><identifier>ISSN: 0048-9697</identifier><identifier>EISSN: 1879-1026</identifier><identifier>DOI: 10.1016/j.scitotenv.2019.02.307</identifier><language>eng</language><publisher>Elsevier B.V</publisher><subject>Apoptosis ; Human embryonic stem cells ; N-acetylcysteine ; Nrf2 pathway ; Oxidative stress ; PM2.5</subject><ispartof>The Science of the total environment, 2019-05, Vol.666, p.713-720</ispartof><rights>2019 Elsevier B.V.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c278t-cb5c15e92d363cc89f7c2fccddd183cfee089761b2a9f78eef5910c18b97c5e3</citedby><cites>FETCH-LOGICAL-c278t-cb5c15e92d363cc89f7c2fccddd183cfee089761b2a9f78eef5910c18b97c5e3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.scitotenv.2019.02.307$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,780,784,3550,27924,27925,45995</link.rule.ids></links><search><creatorcontrib>Jin, Lifang</creatorcontrib><creatorcontrib>Ni, Jian</creatorcontrib><creatorcontrib>Tao, Yuan</creatorcontrib><creatorcontrib>Weng, Xinyi</creatorcontrib><creatorcontrib>Zhu, Yuling</creatorcontrib><creatorcontrib>Yan, Junyan</creatorcontrib><creatorcontrib>Hu, Baowei</creatorcontrib><title>N-acetylcysteine attenuates PM2.5-induced apoptosis by ROS-mediated Nrf2 pathway in human embryonic stem cells</title><title>The Science of the total environment</title><description>While the effects of fine particulate matter (PM2.5) on embryonic toxicity are widely accepted, its exact mechanisms have not yet been fully elucidated, which partially attribute to lack of ideal research model. Embryonic stem cells (ESCs) have the capacity to differentiate into all cell types of three germ layers. Thus, they are ideal resources for the reproductive toxicity assessment in vitro. In the present study, we investigated the effects of PM2.5 exposure on the oxidative stress and apoptosis of human ESCs (hESCs) and its possible mechanism. Our results showed that strong cytotoxicity high reactive oxygen species (ROS) level and fragmentation of nuclei were observed in the PM2.5-treated hESCs. Meanwhile, up-regulation of apoptosis as well as down-regulation of Nrf2 signaling pathway were also observed after PM2.5 treatment. However, we did not detect significant expression change or phosphorylation of Akt and Erk in PM2.5-treated hESCs. Interestingly, scavenging of PM2.5-induced ROS by N-acetylcysteine (NAC) could block cell apoptosis and rescue the activity of Nrf2 signaling pathway. In conclusion, we demonstrate that PM2.5 is toxic to hESCs by inhibition of ROS-mediated Nrf2 pathway activity. Our findings suggest activation of Nrf2 pathway will help develop new strategies for the prevention and treatment of PM2.5-associated disease.
[Display omitted]
•PM2.5 caused severe cytotoxic effects on hESCs by elevating ROS level.•PM2.5 induced down-regulation of Nrf2 signaling pathway in hESCs.•Akt and Erk pathways were not changed in PM2.5-treated hESCs.•NAC could block cell apoptosis and rescue the activity of Nrf2 signaling pathway.</description><subject>Apoptosis</subject><subject>Human embryonic stem cells</subject><subject>N-acetylcysteine</subject><subject>Nrf2 pathway</subject><subject>Oxidative stress</subject><subject>PM2.5</subject><issn>0048-9697</issn><issn>1879-1026</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</creationdate><recordtype>article</recordtype><recordid>eNqFkE1P3DAQhi1UJLbQ31Afe0lqOyS2jwjxUYkvAXfLGU-EVxsntR1Q_j1ebdUrc5nDPPNq5iHkJ2c1Z7z7va0T-DxlDO-1YFzXTNQNk0dkw5XUFWei-0Y2jJ2rSndanpDvKW1ZKan4hoSHygLmdQdryugDUptL1GIzJvp0L-q28sEtgI7aeZrzlHyi_UqfH1-qEZ0vnKMPcRB0tvntw67UB_q2jDZQHPu4TsEDLckjBdzt0hk5Huwu4Y9__ZS8Xl-9Xt5Wd483fy4v7ioQUuUK-hZ4i1q4pmsAlB4kiAHAOcdVAwMiU1p2vBe2jBTi0GrOgKteS2ixOSW_DrFznP4umLIZfdofYANOSzKiqGmb81aLgsoDCnFKKeJg5uhHG1fDmdkLNlvzX7DZCzZMmCK4bF4cNrE88u4x7jkMRZWPCNm4yX-Z8QmfmYtE</recordid><startdate>20190520</startdate><enddate>20190520</enddate><creator>Jin, Lifang</creator><creator>Ni, Jian</creator><creator>Tao, Yuan</creator><creator>Weng, Xinyi</creator><creator>Zhu, Yuling</creator><creator>Yan, Junyan</creator><creator>Hu, Baowei</creator><general>Elsevier B.V</general><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>20190520</creationdate><title>N-acetylcysteine attenuates PM2.5-induced apoptosis by ROS-mediated Nrf2 pathway in human embryonic stem cells</title><author>Jin, Lifang ; Ni, Jian ; Tao, Yuan ; Weng, Xinyi ; Zhu, Yuling ; Yan, Junyan ; Hu, Baowei</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c278t-cb5c15e92d363cc89f7c2fccddd183cfee089761b2a9f78eef5910c18b97c5e3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2019</creationdate><topic>Apoptosis</topic><topic>Human embryonic stem cells</topic><topic>N-acetylcysteine</topic><topic>Nrf2 pathway</topic><topic>Oxidative stress</topic><topic>PM2.5</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Jin, Lifang</creatorcontrib><creatorcontrib>Ni, Jian</creatorcontrib><creatorcontrib>Tao, Yuan</creatorcontrib><creatorcontrib>Weng, Xinyi</creatorcontrib><creatorcontrib>Zhu, Yuling</creatorcontrib><creatorcontrib>Yan, Junyan</creatorcontrib><creatorcontrib>Hu, Baowei</creatorcontrib><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>The Science of the total environment</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Jin, Lifang</au><au>Ni, Jian</au><au>Tao, Yuan</au><au>Weng, Xinyi</au><au>Zhu, Yuling</au><au>Yan, Junyan</au><au>Hu, Baowei</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>N-acetylcysteine attenuates PM2.5-induced apoptosis by ROS-mediated Nrf2 pathway in human embryonic stem cells</atitle><jtitle>The Science of the total environment</jtitle><date>2019-05-20</date><risdate>2019</risdate><volume>666</volume><spage>713</spage><epage>720</epage><pages>713-720</pages><issn>0048-9697</issn><eissn>1879-1026</eissn><abstract>While the effects of fine particulate matter (PM2.5) on embryonic toxicity are widely accepted, its exact mechanisms have not yet been fully elucidated, which partially attribute to lack of ideal research model. Embryonic stem cells (ESCs) have the capacity to differentiate into all cell types of three germ layers. Thus, they are ideal resources for the reproductive toxicity assessment in vitro. In the present study, we investigated the effects of PM2.5 exposure on the oxidative stress and apoptosis of human ESCs (hESCs) and its possible mechanism. Our results showed that strong cytotoxicity high reactive oxygen species (ROS) level and fragmentation of nuclei were observed in the PM2.5-treated hESCs. Meanwhile, up-regulation of apoptosis as well as down-regulation of Nrf2 signaling pathway were also observed after PM2.5 treatment. However, we did not detect significant expression change or phosphorylation of Akt and Erk in PM2.5-treated hESCs. Interestingly, scavenging of PM2.5-induced ROS by N-acetylcysteine (NAC) could block cell apoptosis and rescue the activity of Nrf2 signaling pathway. In conclusion, we demonstrate that PM2.5 is toxic to hESCs by inhibition of ROS-mediated Nrf2 pathway activity. Our findings suggest activation of Nrf2 pathway will help develop new strategies for the prevention and treatment of PM2.5-associated disease.
[Display omitted]
•PM2.5 caused severe cytotoxic effects on hESCs by elevating ROS level.•PM2.5 induced down-regulation of Nrf2 signaling pathway in hESCs.•Akt and Erk pathways were not changed in PM2.5-treated hESCs.•NAC could block cell apoptosis and rescue the activity of Nrf2 signaling pathway.</abstract><pub>Elsevier B.V</pub><doi>10.1016/j.scitotenv.2019.02.307</doi><tpages>8</tpages></addata></record> |
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subjects | Apoptosis Human embryonic stem cells N-acetylcysteine Nrf2 pathway Oxidative stress PM2.5 |
title | N-acetylcysteine attenuates PM2.5-induced apoptosis by ROS-mediated Nrf2 pathway in human embryonic stem cells |
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