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Low dose inhalation of hydrogen sulfide (H<jats:sub>2<\/jats:sub>S) during mechanical ventilation has been proven to prevent lung damage by limiting inflammatory responses in rodent models. However, the capacity of H<jats:sub>2<\/jats:sub>S to affect oxidative processes in VILI and its underlying molecular signaling pathways remains elusive. In the present study we show that ventilation with moderate tidal volumes of 12\u2009ml\/kg for 6\u2009h led to an excessive formation of reactive oxygen species (ROS) in mice lungs which was prevented by supplemental inhalation of 80 parts per million of H<jats:sub>2<\/jats:sub>S. In addition, phosphorylation of the signaling protein Akt was induced by H<jats:sub>2<\/jats:sub>S. In contrast, inhibition of Akt by LY294002 during ventilation reestablished lung damage, neutrophil influx, and proinflammatory cytokine release despite the presence of H<jats:sub>2<\/jats:sub>S. Moreover, the ability of H<jats:sub>2<\/jats:sub>S to induce the antioxidant glutathione and to prevent ROS production was reversed in the presence of the Akt inhibitor. Here, we provide the first evidence that H<jats:sub>2<\/jats:sub>S\u2010mediated Akt activation is a key step in protection against VILI, suggesting that Akt signaling limits not only inflammatory but also detrimental oxidative processes that promote the development of lung injury.<\/jats:p>","DOI":"10.1155\/2017\/3715037","type":"journal-article","created":{"date-parts":[[2017,1,31]],"date-time":"2017-01-31T21:11:26Z","timestamp":1485897086000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":43,"title":["Hydrogen Sulfide Prevents Formation of Reactive Oxygen Species through PI3K\/Akt Signaling and Limits Ventilator\u2010Induced Lung Injury"],"prefix":"10.1155","volume":"2017","author":[{"given":"Sashko Georgiev","family":"Spassov","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rosa","family":"Donus","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul Mikael","family":"Ihle","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helen","family":"Engelstaedter","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander","family":"Hoetzel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5345-8523","authenticated-orcid":false,"given":"Simone","family":"Faller","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2017,1,31]]},"reference":[{"key":"e_1_2_8_1_2","doi-asserted-by":"publisher","DOI":"10.1097\/ccm.0000000000001189"},{"key":"e_1_2_8_2_2","doi-asserted-by":"publisher","DOI":"10.1097\/aln.0000000000000706"},{"key":"e_1_2_8_3_2","doi-asserted-by":"publisher","DOI":"10.1055\/s-2006-948289"},{"key":"e_1_2_8_4_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajplung.00069.2005"},{"key":"e_1_2_8_5_2","doi-asserted-by":"publisher","DOI":"10.1097\/00075198-200502000-00013"},{"key":"e_1_2_8_6_2","doi-asserted-by":"publisher","DOI":"10.1056\/nejm200005043421801"},{"key":"e_1_2_8_7_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrd2425"},{"key":"e_1_2_8_8_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00134-010-2022-2"},{"key":"e_1_2_8_9_2","doi-asserted-by":"publisher","DOI":"10.1097\/ALN.0b013e3181de7107"},{"key":"e_1_2_8_10_2","doi-asserted-by":"publisher","DOI":"10.1097\/ALN.0b013e31823306cf"},{"key":"e_1_2_8_11_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0102401"},{"key":"e_1_2_8_12_2","doi-asserted-by":"publisher","DOI":"10.1213\/ANE.0b013e31824762f0"},{"key":"e_1_2_8_13_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00134-010-2018-y"},{"key":"e_1_2_8_14_2","doi-asserted-by":"publisher","DOI":"10.1186\/cc6101"},{"key":"e_1_2_8_15_2","doi-asserted-by":"publisher","DOI":"10.1097\/01.CCM.0000190909.70601.2C"},{"key":"e_1_2_8_16_2","doi-asserted-by":"publisher","DOI":"10.1038\/aps.2009.190"},{"key":"e_1_2_8_17_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-physiol-020911-153324"},{"key":"e_1_2_8_18_2","doi-asserted-by":"publisher","DOI":"10.2174\/1381612811319150006"},{"key":"e_1_2_8_19_2","doi-asserted-by":"publisher","DOI":"10.1213\/ane.0000000000001296"},{"key":"e_1_2_8_20_2","doi-asserted-by":"publisher","DOI":"10.1089\/ars.2008.2231"},{"key":"e_1_2_8_21_2","doi-asserted-by":"publisher","DOI":"10.3109\/10408448409029321"},{"key":"e_1_2_8_22_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1108581"},{"key":"e_1_2_8_23_2","doi-asserted-by":"publisher","DOI":"10.1186\/2045-9912-2-26"},{"key":"e_1_2_8_24_2","doi-asserted-by":"publisher","DOI":"10.1165\/rcmb.2011-0248OC"},{"key":"e_1_2_8_25_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajplung.00010.2008"},{"key":"e_1_2_8_26_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00432.2010"},{"key":"e_1_2_8_27_2","first-page":"93","volume-title":"Methods in Enzymology","author":"Zuidema M. 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