{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T16:21:00Z","timestamp":1782836460526,"version":"3.54.5"},"reference-count":0,"publisher":"The Nencki Institute of Experimental Biology, Polish Academy of Sciences","issue":"3","license":[{"start":{"date-parts":[[2022,9,30]],"date-time":"2022-09-30T00:00:00Z","timestamp":1664496000000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Acta Neurobiol. Exp."],"abstract":"<jats:p>Hypoxia inducible factor 1\u03b1 (HIF\u20111\u03b1) has been reported to play a key role in protecting neurons from ischaemic injury. However, the exact molecular mechanisms remain largely unclear. PC12 cells were exposed to oxygen glucose deprivation\/reoxygenation (OGD\/R) conditions to mimic ischaemic injury in vitro. The expression of the HIF\u20111\u03b1 mRNA, miR\u201120a\u20115p, and kinesin family member 5A (KIF5A) mRNA was tested using qRT\u2013PCR. Levels of the HIF\u20111\u03b1, LC3I\/II, P62, LAMP2, cathepsin B (CTSB) and KIF5A proteins were determined\nusing western blotting. The CCK\u20118 assay was conducted to assess PC12 cell viability. DQ\u2011Red\u2011BSA and LysoSensor Green DND\u2011189 dyes were employed to measure the proteolytic activity and pH of lysosomes, respectively. The interaction between miR\u201120a\u20115p and HIF\u20111\u03b1 or KIF5A was verified by performing chromatin immunoprecipitation (ChIP) and\/or dual\u2011luciferase reporter assays. TUNEL staining was adopted to assess PC12 cell death. GFP\u2011LC3 and RFP\u2011GFP\u2011LC3 probes were used to examine the autophagy status and autophagy\nflux of PC12 cells. A rat middle cerebral artery occlusion\u2011reperfusion (MCAO\/R) model was established to investigate the role of the HIF\u20111\u03b1\/miR\u201120a\u20115p\/KIF5A axis in ischaemic stroke in vivo. OGD\/R exposure initiated PC12 cell autophagy and injury. HIF\u20111\u03b1 expression was substantially increased in PC12 cells after OGD\/R exposure. Overexpression of HIF\u20111\u03b1 reversed the effects of OGD\/R on reducing cell viability, blocking autophagy flux and inducing lysosome dysfunction. These rescue effects of HIF\u20111\u03b1 depended on KIF5A. HIF\u20111\u03b1\nnegatively regulated miR\u201120a\u20115p expression by targeting its promoter region, and miR\u201120a\u20115p directly targeted and negatively regulated the KIF5A mRNA. Overexpression of miR\u201120a\u20115p abolished the effects of HIF\u20111\u03b1 on rescuing OGD\/R\u2011induced injury in PC12 cells. The effects of the HIF\u20111\u03b1\/miR\u201120a\u20115p\/KIF5A axis were verified in MCAO\/R rats. HIF\u20111\u03b1 protects PC12 cells from OGD\/R\u2011induced cell injury by regulating autophagy flux through the miR\u201120a\u20115p\/KIF5A axis.<\/jats:p>","DOI":"10.55782\/ane-2022-034","type":"journal-article","created":{"date-parts":[[2022,10,7]],"date-time":"2022-10-07T13:22:30Z","timestamp":1665148950000},"page":"358-372","source":"Crossref","is-referenced-by-count":6,"title":["HIF\u20111\u03b1 protects PC12 cells from OGD\/R\u2011induced cell injury by regulating autophagy flux through the miR\u201120a\u20115p\/KIF5A axis"],"prefix":"10.55782","volume":"82","author":[{"given":"Jing\u2011Wei","family":"Cao","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhan\u2011Bin","family":"Tang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ji\u2011He","family":"Song","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jia\u2011Lin","family":"Yao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao\u2011Meng","family":"Sheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhi\u2011Qiang","family":"Su","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"34635","published-online":{"date-parts":[[2022,9,30]]},"container-title":["Acta Neurobiologiae Experimentalis"],"original-title":[],"link":[{"URL":"https:\/\/ane.pl\/index.php\/ane\/article\/download\/2356\/2348","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/ane.pl\/index.php\/ane\/article\/download\/2356\/2348","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,5,23]],"date-time":"2024-05-23T14:45:41Z","timestamp":1716475541000},"score":1,"resource":{"primary":{"URL":"https:\/\/ane.pl\/index.php\/ane\/article\/view\/2356"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,9,30]]},"references-count":0,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2022,9,30]]}},"URL":"https:\/\/doi.org\/10.55782\/ane-2022-034","relation":{},"ISSN":["1689-0035","0065-1400"],"issn-type":[{"value":"1689-0035","type":"electronic"},{"value":"0065-1400","type":"print"}],"subject":[],"published":{"date-parts":[[2022,9,30]]}}}