{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,23]],"date-time":"2026-07-23T02:21:29Z","timestamp":1784773289831,"version":"3.55.0"},"reference-count":61,"publisher":"SAGE Publications","issue":"2","license":[{"start":{"date-parts":[[2017,5,3]],"date-time":"2017-05-03T00:00:00Z","timestamp":1493769600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Dose-Response"],"published-print":{"date-parts":[[2017,6,1]]},"abstract":"<jats:p>\n                    Kelch-like ECH-associated protein 1 (Keap1), nuclear factor erythroid 2-like factor 2-related factor 2 (Nrf2), and the antioxidant response element (ARE) are interacting components of a master regulatory signaling pathway that coordinates redox homeostasis, cytoprotective responses, and shifts in stem cell state. This study reexamined detailed dose\u2013response (DR) data reported for in vitro Nrf2-ARE activation in human hepatoblastoma HepG2 cell lines containing either a ARE- bla or ARE- luc reporter at 12 different concentrations of each of 15 chemicals. The normalized study data were combined among chemicals exhibiting a positive response, yielding n = 531 (179) DR data for 9 (7) chemicals using the ARE- bla (ARE- luc) assay. Three-parameter linear\/ kth-power regression fits obtained to each combined set of ARE- bla- or ARE- luc-assay response data provided good fits ( R\n                    <jats:sup>2<\/jats:sup>\n                    = .99 or .91, respectively, P\n                    <jats:sub>fit<\/jats:sub>\n                    &gt; .99) that each incorporate a highly significant negative initial linear slope ( P = 4 \u00d7 10\n                    <jats:sup>\u22125<\/jats:sup>\n                    or .00025) and an overall J-shaped DR pattern. Results from this reanalysis of high-resolution ARE response data support the hypothesis that nonlinear ARE-mediated adaptive cellular responses to oxidative stress are governed by an ultrasensitive molecular switch.\n                  <\/jats:p>","DOI":"10.1177\/1559325817699696","type":"journal-article","created":{"date-parts":[[2017,5,3]],"date-time":"2017-05-03T03:07:39Z","timestamp":1493780859000},"page":"155932581769969","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":14,"title":["Low-Dose Dose\u2013Response for In Vitro Nrf2-ARE Activation in Human HepG2 Cells"],"prefix":"10.1177","volume":"15","author":[{"given":"Kenneth T.","family":"Bogen","sequence":"first","affiliation":[{"name":"Exponent Health Sciences, Oakland, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2017,5,3]]},"reference":[{"key":"bibr1-1559325817699696","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.pharmtox.46.120604.141046"},{"key":"bibr2-1559325817699696","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.R900010200"},{"key":"bibr3-1559325817699696","doi-asserted-by":"publisher","DOI":"10.1096\/fj.09-133520"},{"key":"bibr4-1559325817699696","doi-asserted-by":"publisher","DOI":"10.1093\/carcin\/bgp231"},{"issue":"3","key":"bibr5-1559325817699696","first-page":"395","volume":"26","author":"Sesti F","year":"2012","journal-title":"In Vivo"},{"key":"bibr6-1559325817699696","doi-asserted-by":"publisher","DOI":"10.1016\/j.bcp.2012.11.016"},{"key":"bibr7-1559325817699696","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-pharmtox-011112-140320"},{"key":"bibr8-1559325817699696","doi-asserted-by":"publisher","DOI":"10.1016\/j.tibs.2014.02.002"},{"issue":"1","key":"bibr9-1559325817699696","first-page":"1","volume":"67","author":"Pall ML","year":"2015","journal-title":"Acta Physiologica Sinica"},{"key":"bibr10-1559325817699696","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2015.06.021"},{"key":"bibr11-1559325817699696","doi-asserted-by":"publisher","DOI":"10.1002\/mc.20465"},{"key":"bibr12-1559325817699696","doi-asserted-by":"publisher","DOI":"10.1172\/JCI200418699"},{"key":"bibr13-1559325817699696","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1002890107"},{"key":"bibr14-1559325817699696","doi-asserted-by":"publisher","DOI":"10.1021\/jm101445p"},{"key":"bibr15-1559325817699696","doi-asserted-by":"publisher","DOI":"10.1016\/B978-0-12-405882-8.00004-0"},{"key":"bibr16-1559325817699696","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurobiolaging.2015.10.016"},{"key":"bibr17-1559325817699696","doi-asserted-by":"publisher","DOI":"10.1093\/toxsci\/kfv213"},{"key":"bibr18-1559325817699696","doi-asserted-by":"publisher","DOI":"10.2174\/1875397301105010001"},{"key":"bibr19-1559325817699696","doi-asserted-by":"publisher","DOI":"10.1289\/ehp.1104709"},{"key":"bibr20-1559325817699696","doi-asserted-by":"publisher","DOI":"10.1126\/science.1154619"},{"key":"bibr21-1559325817699696","doi-asserted-by":"publisher","DOI":"10.1016\/j.drudis.2010.07.007"},{"key":"bibr22-1559325817699696","unstructured":"Kendall M, Stuart A. 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