{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,6]],"date-time":"2026-02-06T05:46:11Z","timestamp":1770356771351,"version":"3.49.0"},"reference-count":44,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2017,12,31]],"date-time":"2017-12-31T00:00:00Z","timestamp":1514678400000},"content-version":"vor","delay-in-days":364,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Oxidative Medicine and Cellular Longevity"],"published-print":{"date-parts":[[2017,1]]},"abstract":"<jats:p>Acrolein is known to be involved in acute lung injury and other pulmonary diseases. A number of studies have suggested that acrolein\u2010induced toxic effects are associated with depletion of antioxidants, such as reduced glutathione and protein thiols, and production of reactive oxygen species. Mitochondrial NADP<jats:sup>+<\/jats:sup>\u2010dependent isocitrate dehydrogenase (<jats:italic>idh2<\/jats:italic>) regulates mitochondrial redox balance and reduces oxidative stress\u2010induced cell injury via generation of NADPH. Therefore, we evaluated the role of <jats:italic>idh2<\/jats:italic> in acrolein\u2010induced lung injury using <jats:italic>idh2<\/jats:italic> short hairpin RNA\u2010 (shRNA\u2010) transfected Lewis lung carcinoma (LLC) cells and <jats:italic>idh2<\/jats:italic>\u2010deficient (<jats:italic>idh2<jats:sup>\u2212\/\u2212<\/jats:sup><\/jats:italic>) mice. Downregulation of <jats:italic>idh2<\/jats:italic> expression increased susceptibility to acrolein via induction of apoptotic cell death due to elevated mitochondrial oxidative stress. <jats:italic>Idh2<\/jats:italic> deficiency also promoted acrolein\u2010induced lung injury in <jats:italic>idh2<\/jats:italic> knockout mice through the disruption of mitochondrial redox status. In addition, acrolein\u2010induced toxicity in <jats:italic>idh2<\/jats:italic> shRNA\u2010transfected LLC cells and in <jats:italic>idh2<\/jats:italic> knockout mice was ameliorated by the antioxidant, N\u2010acetylcysteine, through attenuation of oxidative stress resulting from <jats:italic>idh2<\/jats:italic> deficiency. In conclusion, <jats:italic>idh2<\/jats:italic> deficiency leads to mitochondrial redox environment deterioration, which causes acrolein\u2010mediated apoptosis of LLC cells and acrolein\u2010induced lung injury in <jats:italic>idh2<jats:sup>\u2212\/\u2212<\/jats:sup><\/jats:italic> mice. The present study supports the central role of <jats:italic>idh2<\/jats:italic> deficiency in inducing oxidative stress resulting from acrolein\u2010induced disruption of mitochondrial redox status in the lung.<\/jats:p>","DOI":"10.1155\/2017\/1595103","type":"journal-article","created":{"date-parts":[[2017,12,31]],"date-time":"2017-12-31T23:30:57Z","timestamp":1514763057000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["<i>Idh2<\/i> Deficiency Exacerbates Acrolein\u2010Induced Lung Injury through Mitochondrial Redox Environment Deterioration"],"prefix":"10.1155","volume":"2017","author":[{"given":"Jung Hyun","family":"Park","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hyeong Jun","family":"Ku","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6437-5157","authenticated-orcid":false,"given":"Jin Hyup","family":"Lee","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0543-4321","authenticated-orcid":false,"given":"Jeen-Woo","family":"Park","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2017,12,31]]},"reference":[{"key":"e_1_2_7_1_2","doi-asserted-by":"publisher","DOI":"10.3109\/10408448509037461"},{"key":"e_1_2_7_2_2","doi-asserted-by":"publisher","DOI":"10.1289\/ehp.9410289"},{"key":"e_1_2_7_3_2","doi-asserted-by":"publisher","DOI":"10.1164\/ajrccm.160.supplement_1.6"},{"key":"e_1_2_7_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.taap.2012.09.021"},{"key":"e_1_2_7_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.taap.2009.01.024"},{"key":"e_1_2_7_6_2","doi-asserted-by":"publisher","DOI":"10.1093\/toxsci\/57.1.6"},{"key":"e_1_2_7_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/0891-5849(91)90192-6"},{"key":"e_1_2_7_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/0891-5849(89)90137-8"},{"key":"e_1_2_7_9_2","doi-asserted-by":"publisher","DOI":"10.1093\/carcin\/6.12.1755"},{"key":"e_1_2_7_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/0891-5849(93)90058-3"},{"key":"e_1_2_7_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2013.06.008"},{"key":"e_1_2_7_12_2","doi-asserted-by":"publisher","DOI":"10.2353\/ajpath.2007.070218"},{"key":"e_1_2_7_13_2","doi-asserted-by":"publisher","DOI":"10.1165\/rcmb.2010-0249OC"},{"key":"e_1_2_7_14_2","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.06-0248"},{"key":"e_1_2_7_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuint.2005.07.002"},{"key":"e_1_2_7_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2005.02.001"},{"key":"e_1_2_7_17_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-genet-110410-132529"},{"key":"e_1_2_7_18_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.pharmtox.47.120505.105122"},{"key":"e_1_2_7_19_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.cdd.4401420"},{"key":"e_1_2_7_20_2","doi-asserted-by":"publisher","DOI":"10.1096\/fj.00-0823hyp"},{"key":"e_1_2_7_21_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M010120200"},{"key":"e_1_2_7_22_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M700303200"},{"key":"e_1_2_7_23_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0891-5849(02)00815-8"},{"key":"e_1_2_7_24_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0014-5793(00)01587-8"},{"key":"e_1_2_7_25_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2007.07.009"},{"key":"e_1_2_7_26_2","doi-asserted-by":"publisher","DOI":"10.1016\/0076-6879(95)60154-6"},{"key":"e_1_2_7_27_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2014.12.018"},{"key":"e_1_2_7_28_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0038038"},{"key":"e_1_2_7_29_2","first-page":"233","article-title":"Pulmonary effects of continuous endotoxin infusion in the rat","volume":"33","author":"Simons R. K.","year":"1991","journal-title":"Circulatory Shock"},{"key":"e_1_2_7_30_2","doi-asserted-by":"publisher","DOI":"10.1006\/excr.2000.4836"},{"key":"e_1_2_7_31_2","doi-asserted-by":"publisher","DOI":"10.1023\/B:MCBI.0000049134.69131.89"},{"key":"e_1_2_7_32_2","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00018.2001"},{"key":"e_1_2_7_33_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.biocel.2006.07.001"},{"key":"e_1_2_7_34_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0503251102"},{"key":"e_1_2_7_35_2","doi-asserted-by":"publisher","DOI":"10.1021\/tx015552p"},{"key":"e_1_2_7_36_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajplung.00227.2005"},{"key":"e_1_2_7_37_2","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1098-1136(200006)30:4<329::AID-GLIA20>3.0.CO;2-R"},{"key":"e_1_2_7_38_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-2952(02)01174-7"},{"key":"e_1_2_7_39_2","doi-asserted-by":"publisher","DOI":"10.1006\/abbi.1994.1167"},{"key":"e_1_2_7_40_2","doi-asserted-by":"publisher","DOI":"10.1006\/abbi.1999.1509"},{"key":"e_1_2_7_41_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0005-2728(98)00112-1"},{"key":"e_1_2_7_42_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1104343"},{"key":"e_1_2_7_43_2","doi-asserted-by":"publisher","DOI":"10.1016\/0891-5849(89)90066-X"},{"key":"e_1_2_7_44_2","doi-asserted-by":"publisher","DOI":"10.1080\/10715762.2016.1185519"}],"container-title":["Oxidative Medicine and Cellular Longevity"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/downloads.hindawi.com\/journals\/omcl\/2017\/1595103.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/downloads.hindawi.com\/journals\/omcl\/2017\/1595103.xml","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1155\/2017\/1595103","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,8,6]],"date-time":"2024-08-06T04:52:54Z","timestamp":1722919974000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1155\/2017\/1595103"}},"subtitle":[],"editor":[{"given":"Daniela","family":"Giustarini","sequence":"additional","affiliation":[],"role":[{"role":"editor","vocabulary":"crossref"}]}],"short-title":[],"issued":{"date-parts":[[2017,1]]},"references-count":44,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2017,1]]}},"alternative-id":["10.1155\/2017\/1595103"],"URL":"https:\/\/doi.org\/10.1155\/2017\/1595103","archive":["Portico"],"relation":{},"ISSN":["1942-0900","1942-0994"],"issn-type":[{"value":"1942-0900","type":"print"},{"value":"1942-0994","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,1]]},"assertion":[{"value":"2017-07-27","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2017-11-01","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2017-12-31","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"1595103"}}