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Both hypoxic preconditioning and pharmacological induction of the cellular hypoxic response can drive cellular adaptations and improve transplant survival in a number of disease\/injury models. Hypoxia\u2010inducible factor 1 alpha (HIF\u20101\u03b1), a regulator of the cellular response to hypoxia, is implicated in preconditioning\u2010associated protection. HIF\u20101\u03b1 cellular levels are regulated by the HIF\u2010prolyl hydroxylases (HIF\u2010PHDs). Pharmacological inhibition of the HIF\u2010PHDs mimics hypoxic preconditioning and provides a method to induce adaptive hypoxic responses without direct exposure to hypoxia. In this study, we show that hypoxia\u2010mimetics, deferoxamine (DFO) and adaptaquin (AQ), enhance HIF\u20101\u03b1 stability and HIF\u20101\u03b1 target gene expression. Expression profiling of hypoxia\u2010related genes demonstrates that HIF\u2010dependent and HIF\u2010independent expression changes occur. Analyses of transcription factor binding sites identify several candidate transcriptional co\u2010regulators that vary in SCs along with HIF\u20101\u03b1. Using an in vitro model system, we show that hypoxia\u2010mimetics are potent blockers of oxidative stress\u2010induced death in SCs. In contrast, traditional hypoxic preconditioning was not protective. The robust protection induced by pharmacological preconditioning, particularly with DFO, indicates that pharmacological induction of hypoxic adaptations could be useful for promoting transplanted SC survival. These agents may also be more broadly useful for protecting SCs, as oxidative stress is a major pathway that drives cellular damage in the context of neurological injury and disease, including demyelinating diseases and peripheral neuropathies.<\/jats:p>","DOI":"10.1002\/glia.24019","type":"journal-article","created":{"date-parts":[[2021,5,21]],"date-time":"2021-05-21T14:16:31Z","timestamp":1621606591000},"page":"2215-2234","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Treatment with hypoxia\u2010mimetics protects cultured rat Schwann cells against oxidative stress\u2010induced cell death"],"prefix":"10.1002","volume":"69","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8470-802X","authenticated-orcid":false,"given":"Brian T.","family":"David","sequence":"first","affiliation":[{"name":"Burke Neurological Institute  White Plains New York USA"},{"name":"Weill Cornell Medicine Feil Family Brain and Mind Research Institute  New York New York USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3529-2168","authenticated-orcid":false,"given":"Jessica J.","family":"Curtin","sequence":"additional","affiliation":[{"name":"Burke Neurological Institute  White Plains New York USA"},{"name":"Weill Cornell Medicine Feil Family Brain and Mind Research Institute  New York New York USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7525-5986","authenticated-orcid":false,"given":"Jennifer L.","family":"Brown","sequence":"additional","affiliation":[{"name":"Burke Neurological Institute  White Plains New York USA"},{"name":"Weill Cornell Medicine Feil Family Brain and Mind Research Institute  New York New York USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0527-007X","authenticated-orcid":false,"given":"David J. 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