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At 100\u2009\u00b5M, the PHD inhibitors did not cause cytotoxicity and apoptosis. MTT activity was only significantly reduced by FG4592 or Bayer 85\u20133934 in PC12 cells. The PHD inhibitors at 100\u2009\u00b5M significantly increased the LC3-II\/LC3-I expression ratio and downregulated p62 in PC12 cells, so did FG4592 (30\u2009\u00b5M) and DMOG (100\u2009\u00b5M) in neurons. HIF-1\u03b1 was stabilised in PC12 cells by all the PHD inhibitors at 100\u2009\u00b5M except for DMOG, which stabilised HIF-1\u03b1 at 1 and 2\u2009mM. In primary neurons, HIF-1\u03b1 was stabilised by FG4592 (30\u2009\u00b5M) and DMOG (100\u2009\u00b5M). Pretreatment with the PHD inhibitors 24\u2009hours followed by 24\u2009hour reoxygenation prior to 6\u2009hours OGD (0.3% O<jats:sub>2<\/jats:sub>) significantly reduced LDH release and increased MTT activity compared to vehicle (1% DMSO) pretreatment. In conclusion, the PHD inhibitors stabilise HIF-1\u03b1 in normoxia, induce autophagy, and protect cells from a subsequent OGD insult. The new class of PHD inhibitors (FG4592, FG2216, GSK1278863, Bay85-3934) have the higher potency than DMOG. The interplay between autophagy, HIF stabilisation and neuroprotection in ischaemic stroke merits further investigation.<\/jats:p>","DOI":"10.1038\/s41598-020-58482-w","type":"journal-article","created":{"date-parts":[[2020,1,31]],"date-time":"2020-01-31T11:02:58Z","timestamp":1580468578000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":57,"title":["Hypoxia-inducible factor (HIF) prolyl hydroxylase inhibitors induce autophagy and have a protective effect in an in-vitro ischaemia model"],"prefix":"10.1038","volume":"10","author":[{"given":"Ayesha","family":"Singh","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James W.","family":"Wilson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0290-6565","authenticated-orcid":false,"given":"Christopher J.","family":"Schofield","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8745-5902","authenticated-orcid":false,"given":"Ruoli","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2020,1,31]]},"reference":[{"issue":"8","key":"58482_CR1","doi-asserted-by":"crossref","first-page":"773","DOI":"10.1002\/cmdc.201600012","volume":"11","author":"SE Wilkins","year":"2016","unstructured":"Wilkins, S. 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