{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T03:41:37Z","timestamp":1777434097696,"version":"3.51.4"},"reference-count":60,"publisher":"SAGE Publications","issue":"4","license":[{"start":{"date-parts":[[2015,2,1]],"date-time":"2015-02-01T00:00:00Z","timestamp":1422748800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Antioxidants & Redox Signaling"],"published-print":{"date-parts":[[2015,2]]},"abstract":"\n \n Aims:<\/jats:italic>\n <\/jats:bold>\n Nrf2 is a master transcription factor for antioxidant response element (ARE)-mediated cytoprotective gene induction. A protective role for pulmonary\n Nrf2<\/jats:italic>\n was determined in model oxidative disorders, including hyperoxia-induced acute lung injury (ALI). To obtain additional insights into the function and genetic regulation of\n Nrf2<\/jats:italic>\n , we assessed functional single nucleotide polymorphisms (SNPs) of\n Nrf2<\/jats:italic>\n in inbred mouse strains and tested whether sequence variation is associated with hyperoxia susceptibility.\n \n Results:<\/jats:italic>\n <\/jats:bold>\n Nrf2<\/jats:italic>\n SNPs were compiled from publicly available databases and by re-sequencing DNA from inbred strains. Hierarchical clustering of\n Nrf2<\/jats:italic>\n SNPs categorized the strains into three major haplotypes. Hyperoxia susceptibility was greater in haplotypes 2 and 3 strains than in haplotype 1 strains. A promoter SNP \u2212103\u2009T\/C adding an Sp1 binding site in haplotype 2 diminished promoter activation basally and under hyperoxia. Haplotype 3 mice bearing nonsynonymous coding SNPs located in (1862\u2009A\/T, His543Gln) and adjacent to (1417\u2009T\/C, Thr395Ile) the Neh1 domain showed suppressed nuclear transactivation of pulmonary Nrf2 relative to other strains, and overexpression of haplotype 3\n Nrf2<\/jats:italic>\n showed lower ARE responsiveness than overexpression of haplotype 1\n Nrf2<\/jats:italic>\n in airway cells. Importantly, we found a significant correlation of\n Nrf2<\/jats:italic>\n haplotypes and hyperoxic lung injury phenotypes.\n \n Innovation and Conclusion:<\/jats:italic>\n <\/jats:bold>\n The results indicate significant influence of\n Nrf2<\/jats:italic>\n polymorphisms and haplotypes on gene function and hyperoxia susceptibility. Our findings further support\n Nrf2<\/jats:italic>\n as a genetic determinant in ALI pathogenesis and provide useful tools for investigators who use mouse strains classified by\n Nrf2<\/jats:italic>\n haplotypes to elucidate the role for Nrf2 in oxidative disorders.\n Antioxid. Redox Signal<\/jats:italic>\n . 22, 325\u2013338.\n <\/jats:p>","DOI":"10.1089\/ars.2014.5942","type":"journal-article","created":{"date-parts":[[2014,9,30]],"date-time":"2014-09-30T11:43:17Z","timestamp":1412077397000},"page":"325-338","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":27,"title":["Association of\n Nrf2<\/i>\n Polymorphism Haplotypes with Acute Lung Injury Phenotypes in Inbred Strains of Mice"],"prefix":"10.1177","volume":"22","author":[{"given":"Hye-Youn","family":"Cho","sequence":"first","affiliation":[{"name":"National Institutes of Health"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anne E.","family":"Jedlicka","sequence":"additional","affiliation":[{"name":"Johns Hopkins University Bloomberg School of Public Health"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wesley","family":"Gladwell","sequence":"additional","affiliation":[{"name":"National Institutes of Health"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jacqui","family":"Marzec","sequence":"additional","affiliation":[{"name":"National Institutes of Health"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zackary R.","family":"McCaw","sequence":"additional","affiliation":[{"name":"National Institutes of Health"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rachelle J.","family":"Bienstock","sequence":"additional","affiliation":[{"name":"National Institutes of Health"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Steven R.","family":"Kleeberger","sequence":"additional","affiliation":[{"name":"National Institutes of Health"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"179","published-online":{"date-parts":[[2015,2,1]]},"reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/25.17.3389"},{"key":"e_1_3_3_3_2","first-page":"211","article-title":"The influence of promoter polymorphism of nuclear factor-erythroid 2-related factor 2 gene on the aberrant DNA methylation in gastric epithelium","volume":"19","author":"Arisawa T","year":"2008","unstructured":"Arisawa T, , Tahara T, , Shibata T, , Nagasaka M, , Nakamura M, , Kamiya Y, , Fujita H, , Yoshioka D, , Arima Y, , Okubo M, , Hirata I, , and Nakano H. The influence of promoter polymorphism of nuclear factor-erythroid 2-related factor 2 gene on the aberrant DNA methylation in gastric epithelium. 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