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However, recent studies demonstrate that the effect of cyanide on Complex IV in various mammalian cells is biphasic: in lower concentrations (nanomolar to low micromolar) cyanide stimulates Complex IV activity, increases ATP production and accelerates cell proliferation, while at higher concentrations (high micromolar to low millimolar) it produces the previously known (\u2018classic\u2019) toxic effects. The first part of the article describes the cytotoxic actions of cyanide in the context of environmental toxicology, and highlights pathophysiological conditions (e.g., cystic fibrosis with\n                    <jats:italic>Pseudomonas<\/jats:italic>\n                    colonization) where bacterially produced cyanide exerts deleterious effects to the host. The second part of the article summarizes the mammalian sources of cyanide production and overviews the emerging concept that mammalian cells may produce cyanide, in low concentrations, to serve biological regulatory roles. Cyanide fulfills many of the general criteria as a \u2018classical\u2019 mammalian gasotransmitter and shares some common features with the current members of this class: nitric oxide, carbon monoxide, and hydrogen sulfide.\n                  <\/jats:p>","DOI":"10.1111\/febs.16135","type":"journal-article","created":{"date-parts":[[2021,7,23]],"date-time":"2021-07-23T15:11:45Z","timestamp":1627053105000},"page":"2481-2515","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":105,"title":["The two faces of cyanide: an environmental toxin and a potential novel mammalian gasotransmitter"],"prefix":"10.1111","volume":"289","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0186-1817","authenticated-orcid":false,"given":"Karim","family":"Zuhra","sequence":"first","affiliation":[{"name":"Chair of Pharmacology Section\u00a0of Medicine University of Fribourg  Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3110-4235","authenticated-orcid":false,"given":"Csaba","family":"Szabo","sequence":"additional","affiliation":[{"name":"Chair of Pharmacology Section\u00a0of Medicine University of Fribourg  Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,8,5]]},"reference":[{"key":"e_1_2_15_2_1","doi-asserted-by":"publisher","DOI":"10.1093\/jxb\/ern089"},{"key":"e_1_2_15_3_1","doi-asserted-by":"publisher","DOI":"10.4161\/psb.27612"},{"key":"e_1_2_15_4_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12870-019-1690-5"},{"key":"e_1_2_15_5_1","doi-asserted-by":"publisher","DOI":"10.1104\/pp.18.01083"},{"key":"e_1_2_15_6_1","doi-asserted-by":"publisher","DOI":"10.1093\/jxb\/erz225"},{"key":"e_1_2_15_7_1","doi-asserted-by":"publisher","DOI":"10.1128\/br.40.3.652-680.1976"},{"key":"e_1_2_15_8_1","doi-asserted-by":"publisher","DOI":"10.1128\/JB.186.20.6837-6844.2004"},{"key":"e_1_2_15_9_1","doi-asserted-by":"publisher","DOI":"10.1007\/s002039900127"},{"key":"e_1_2_15_10_1","doi-asserted-by":"publisher","DOI":"10.1111\/jam.12697"},{"key":"e_1_2_15_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-019-13013-8"},{"key":"e_1_2_15_12_1","doi-asserted-by":"publisher","DOI":"10.1080\/01652176.1980.9693766"},{"key":"e_1_2_15_13_1","unstructured":"SimeonovaFP&FishbeinL(2004)Hydrogen cyanide and cyanides: human health aspects. 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