{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T03:55:25Z","timestamp":1790740525961,"version":"4.1.0"},"reference-count":48,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2019,3,5]],"date-time":"2019-03-05T00:00:00Z","timestamp":1551744000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"The Third Xiangya Hospital of Central South University"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Environmental Toxicology"],"published-print":{"date-parts":[[2019,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>The insecticide exposure has been linked to Parkinson's disease (PD). In the present study, we used a most widely used cell line in study of PD, the SH\u2010SY5Y cells, to investigate mechanisms of chlorpyrifos (CPF) induced cell toxicity and the possible roles of cell pyroptosis and oxidative stress in SH\u2010SY5Y cells, as well as role of miR\u2010181\/SIRT1\/PGC\u20101\u03b1\/Nrf2 signaling pathway in this process.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>SH\u2010SY5Y cells were treated with different concentrations of CPF. Cell viability was measured using CCK\u20108 assay. Cell pyroptosis was determined by immunofluorescence of caspase\u20101 and TUNEL assay. The miR\u2010181 (has\u2010miR\u2010181\u20105p) level was determined by qRT\u2010PCR. Expression of SIRT1, PGC\u20101\u03b1, Nrf2, and pyroptosis related proteins NLRP3, caspase\u20101, IL\u20101\u03b2, and IL\u201018 was determined by both qRT\u2010PCR and Western blotting.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Cell viability was found to be decreased with the increased CPF concentrations. The pyroptosis related proteins, ROS levels, as well as level of caspase\u20101 and the TUNEL positive cells were all significantly up\u2010regulated by CPF. Meanwhile, expression of miR\u2010181 and pyroptosis proteins was also enhanced, while the SIRT1\/PGC\u20101\u03b1\/Nrf2 signaling was inhibited by CPF. Knockdown of Nrf2 significantly up\u2010regulated the expression of pyroptosis related proteins, ROS level, caspase\u20101, and the TUNEL positive cells, while over\u2010expression of Nrf2 resulted in opposite results. The expression of PGC\u20101\u03b1 and Nrf2 was significantly down\u2010regulated when SIRT1 was inhibited, while over\u2010expressed SIRT1 led to increased PGC\u20101\u03b1 and Nrf2 levels. Besides, miR\u2010181 promoted the CPF induced activation of pyroptosis and oxidative stress, as well as down\u2010regulated SIRT1\/PGC\u20101\u03b1\/Nrf2 signaling, while inhibition of miR\u2010181 led to opposite results.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Chlorpyrifos could inhibit cell proliferation, activate cell pyroptosis and increase susceptibility on oxidative stress\u2010induced toxicity by elevating miR\u2010181 through down\u2010regulation of the SIRT1\/PGC\u20101\u03b1\/Nrf2 pathway in human neuroblastoma SH\u2010SY5Y cells. This study might give deeper insights for mechanisms of CPF induced toxicity and might give some novel research targets for PD treatment.<\/jats:p><\/jats:sec>","DOI":"10.1002\/tox.22736","type":"journal-article","created":{"date-parts":[[2019,3,6]],"date-time":"2019-03-06T03:07:33Z","timestamp":1551841653000},"page":"699-707","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":112,"title":["Chlorpyrifos activates cell pyroptosis and increases susceptibility on oxidative stress\u2010induced toxicity by miR\u2010181\/SIRT1\/PGC\u20101\u03b1\/Nrf2 signaling pathway in human neuroblastoma SH\u2010SY5Y cells"],"prefix":"10.1002","volume":"34","author":[{"given":"Meng\u2010Wen","family":"Zhao","sequence":"first","affiliation":[{"name":"Department of Pediatrics The Third Xiangya Hospital of Central South University  Changsha People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pu","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Neurology The Third Xiangya Hospital of Central South University  Changsha People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6872-1336","authenticated-orcid":false,"given":"Ling\u2010Ling","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Pediatrics The Third Xiangya Hospital of Central South University  Changsha People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2019,3,5]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.envpol.2017.04.012"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10311-015-0513-7"},{"issue":"1","key":"e_1_2_7_4_1","first-page":"1","article-title":"Persistence of chlorpyrifos in soils under different moisture regimes","volume":"50","author":"Awasthi MD","year":"2015","journal-title":"Pest Manag Sci"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/tox.22432"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.reprotox.2005.01.012"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1080\/00039890209602934"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1080\/19338244.2017.1317627"},{"key":"e_1_2_7_9_1","first-page":"71","article-title":"Effect of the organophosphate insecticide chlorpyrifos exposure on oxidative stress and quality of Salmo coruhensis spermatozoa","volume":"3","author":"Kutluyer F","year":"2017","journal-title":"Toxin Rev"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tox.2015.09.006"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cub.2016.02.019"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0047299"},{"issue":"42","key":"e_1_2_7_13_1","doi-asserted-by":"crossref","first-page":"44161","DOI":"10.18632\/oncotarget.6592","article-title":"Streptococcus pneumoniaeinduces pyroptosis through the regulation of autophagy in murine microglia","volume":"6","author":"Ji\u2010Yun K","year":"2015","journal-title":"Oncotarget"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainresbull.2017.01.016"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2013.03.019"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2018.03.142"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.3892\/ijmm.2016.2554"},{"issue":"5","key":"e_1_2_7_18_1","first-page":"1","article-title":"1,25(OH)Dimproves cardiac dysfunction, hypertrophy, and fibrosis through PARP1\/SIRT1\/mTOR\u2010related mechanisms in type 1 diabetes","volume":"61","author":"Qu H","year":"2016","journal-title":"Mol Nutr Food Res"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0016-5085(13)64231-6"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1111\/cns.12588"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12640-016-9620-x"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1038\/cddis.2017.467"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00125-012-2539-8"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuro.2012.05.011"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0161-813X(01)00063-8"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.taap.2013.01.013"},{"key":"e_1_2_7_27_1","doi-asserted-by":"publisher","DOI":"10.3892\/ijo.2015.3109"},{"key":"e_1_2_7_28_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsami.5b05347"},{"issue":"256","key":"e_1_2_7_29_1","article-title":"The effect of silica nanoparticle exposure on cultured human keratocytes","volume":"94","author":"Yim B","year":"2016","journal-title":"Acta Ophthalmol Scand"},{"key":"e_1_2_7_30_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12868-015-0175-1"},{"key":"e_1_2_7_31_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0126910"},{"key":"e_1_2_7_32_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep13567"},{"key":"e_1_2_7_33_1","doi-asserted-by":"publisher","DOI":"10.3892\/ijo.2015.2876"},{"key":"e_1_2_7_34_1","doi-asserted-by":"publisher","DOI":"10.1080\/10599240801986215"},{"key":"e_1_2_7_35_1","doi-asserted-by":"publisher","DOI":"10.1097\/EDE.0b013e3181c15ec6"},{"key":"e_1_2_7_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2015.09.010"},{"key":"e_1_2_7_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.virol.2018.05.025"},{"key":"e_1_2_7_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.imbio.2017.10.044"},{"key":"e_1_2_7_39_1","doi-asserted-by":"publisher","DOI":"10.1038\/mi.2016.73"},{"key":"e_1_2_7_40_1","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2017.00351"},{"key":"e_1_2_7_41_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00018-010-0335-5"},{"key":"e_1_2_7_42_1","doi-asserted-by":"publisher","DOI":"10.1002\/eji.201445098"},{"key":"e_1_2_7_43_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10495-018-1499-y"},{"key":"e_1_2_7_44_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12974-018-1064-1"},{"key":"e_1_2_7_45_1","doi-asserted-by":"publisher","DOI":"10.1002\/tox.21918"},{"key":"e_1_2_7_46_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11062-013-9356-7"},{"key":"e_1_2_7_47_1","doi-asserted-by":"publisher","DOI":"10.1111\/jfbc.12530"},{"key":"e_1_2_7_48_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2014.06.010"},{"key":"e_1_2_7_49_1","doi-asserted-by":"publisher","DOI":"10.1002\/biof.1395"}],"container-title":["Environmental Toxicology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Ftox.22736","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/tox.22736","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/tox.22736","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/tox.22736","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,10]],"date-time":"2023-09-10T22:53:48Z","timestamp":1694386428000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/tox.22736"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,3,5]]},"references-count":48,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2019,6]]}},"alternative-id":["10.1002\/tox.22736"],"URL":"https:\/\/doi.org\/10.1002\/tox.22736","archive":["Portico"],"relation":{},"ISSN":["1520-4081","1522-7278"],"issn-type":[{"value":"1520-4081","type":"print"},{"value":"1522-7278","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,3,5]]},"assertion":[{"value":"2018-11-27","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-02-07","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-03-05","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}