{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T08:58:59Z","timestamp":1791190739675,"version":"4.1.0"},"reference-count":46,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2013,5,1]],"date-time":"2013-05-01T00:00:00Z","timestamp":1367366400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2013,5,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Emphysema is caused by the cigarette smoke (CS)\u2013induced destruction of alveolar wall septa, and CS is the main risk factor for chronic obstructive pulmonary disease (COPD). To study the mechanisms of response to this insult, we focused on oxidant-induced lung injury and the potential role of nuclear erythroid 2\u2013related factor\u20132 (Nrf2), which is a key regulator of the antioxidant defense system. We studied the protective role of N-acetylcysteine (NAC) against the injury of alveolar type II (ATII) cells induced by CS in vivo and in vitro. ATII cells were isolated and purified using magnetic MicroBeads (Miltenyi Biotec, Auburn, CA) from Nrf2\u2212\/\u2212 mice and wild-type mice. We analyzed pulmonary injury, inflammation, glutathione (GSH) concentrations, the expression of glutathione cysteine ligase catalytic subunit mRNA, glutathione cysteine ligase modifier subunit mRNA, and glutathione reductase mRNA, and Nrf2, heme oxygenase\u20131, and nicotinamide adenine dinucleotide phosphate\u2013reduced:quinone oxireductase levels by Western blotting, TUNEL assay, and immunocytofluorescence for 4-hydroxynonenal as a marker of oxidative stress. We found that CS induced greater injury in ATII cells obtained from Nrf2\u2212\/\u2212 mice than from wild-type mice. Furthermore, NAC attenuated the injuries by CS in ATII cells obtained from wild-type mice both in vivo and in vitro. Moreover, NAC decreased the injury of ATII cells obtained from Nrf2\u2212\/\u2212 mice. Our results suggest that Nrf2\u2013GSH signaling is important for the protective activity of NAC. In addition, in ATII cells deficient in Nrf2, this compound can provide partial protection through its reactive oxygen species\u2013scavenging activities. Targeting the antioxidant system regulated by Nrf2 may provide an effective strategy against lung injury in COPD.<\/jats:p>","DOI":"10.1165\/rcmb.2012-0295oc","type":"journal-article","created":{"date-parts":[[2013,3,15]],"date-time":"2013-03-15T04:09:02Z","timestamp":1363320542000},"page":"559-567","source":"Crossref","is-referenced-by-count":47,"title":["<i>N<\/i>\n                    -Acetylcysteine Protects Murine Alveolar Type II Cells from Cigarette Smoke Injury in a Nuclear Erythroid 2\u2013Related Factor\u20132\u2013Independent Manner"],"prefix":"10.1093","volume":"48","author":[{"given":"Elise M.","family":"Messier","sequence":"first","affiliation":[{"name":"Department of Medicine, National Jewish Health, Denver, Colorado"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian J.","family":"Day","sequence":"additional","affiliation":[{"name":"Department of Medicine, National Jewish Health, Denver, Colorado"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven R.","family":"Kleeberger","sequence":"additional","affiliation":[{"name":"Laboratory of Respiratory Biology, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rubin M.","family":"Tuder","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Colorado School of Medicine, Denver, Colorado"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Russell P.","family":"Bowler","sequence":"additional","affiliation":[{"name":"Department of Medicine, National Jewish Health, Denver, Colorado"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hong Wei","family":"Chu","sequence":"additional","affiliation":[{"name":"Department of Medicine, National Jewish Health, Denver, Colorado"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert J.","family":"Mason","sequence":"additional","affiliation":[{"name":"Department of Medicine, National Jewish Health, Denver, Colorado"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beata","family":"Kosmider","sequence":"additional","affiliation":[{"name":"Department of Medicine, National Jewish Health, Denver, Colorado"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2013,5,1]]},"reference":[{"key":"2026021904200682000_bib1","doi-asserted-by":"crossref","first-page":"5623","DOI":"10.4049\/jimmunol.1200195","article-title":"NLRC4 inflammasome\u2013mediated production of IL-1beta modulates mucosal immunity in the lung against Gram-negative bacterial infection","volume":"188","author":"Cai","year":"2012","journal-title":"J 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