{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,18]],"date-time":"2026-06-18T13:11:54Z","timestamp":1781788314096,"version":"3.54.5"},"reference-count":60,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2023,5,24]],"date-time":"2023-05-24T00:00:00Z","timestamp":1684886400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Key Research and Development Program of China","award":["2017YFE0129900"],"award-info":[{"award-number":["2017YFE0129900"]}]},{"name":"National Key Research and Development Program of China","award":["31872439"],"award-info":[{"award-number":["31872439"]}]},{"name":"National Natural Science Foundation of China","award":["2017YFE0129900"],"award-info":[{"award-number":["2017YFE0129900"]}]},{"name":"National Natural Science Foundation of China","award":["31872439"],"award-info":[{"award-number":["31872439"]}]},{"name":"Priority Academic Program Development of Jiangsu Higher Education Institutions","award":["2017YFE0129900"],"award-info":[{"award-number":["2017YFE0129900"]}]},{"name":"Priority Academic Program Development of Jiangsu Higher Education Institutions","award":["31872439"],"award-info":[{"award-number":["31872439"]}]},{"name":"Jiangsu Collaborative Innovation Center of Meat Production and Processing, Quality and Safety Control","award":["2017YFE0129900"],"award-info":[{"award-number":["2017YFE0129900"]}]},{"name":"Jiangsu Collaborative Innovation Center of Meat Production and Processing, Quality and Safety Control","award":["31872439"],"award-info":[{"award-number":["31872439"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Ferroptosis participates in the occurrence and development of neurological disorders. Modulating ferroptosis may have therapeutic potential in nervous system diseases. Therefore, TMTbased proteomic analysis in HT-22 cells was performed to identify erastin\u2013induced differentially expressed proteins. The calcium-transporting ATP2B3 (ATP2B3) was screened as a target protein. ATP2B3 knockdown markedly alleviated the erastin\u2013induced decrease in cell viability and elevated ROS (p &lt; 0.01) and reversed the up-regulation of oxidative stress-related proteins polyubiquitin-binding protein p62 (P62), nuclear factor erythroid 2-related factor2 (NRF2), heme oxygenase-1 (HO-1), and NAD(P)H quinone oxidoreductase-1 (NQO1) protein expression (p &lt; 0.05 or p &lt; 0.01) and the down\u2212regulation of Kelch-like ECH-associated protein 1(KEAP1) protein expression (p &lt; 0.01). Moreover, NRF2 knockdown, P62 inhibition, or KEAP1 overexpression rescued the erastin\u2013induced decrease in cell viability (p &lt; 0.05) and increase in ROS production (p &lt; 0.01) in HT-22 cells, while simultaneous overexpression of NRF2 and P62 and knockdown of KEAP1 partially offset the relief effect of ATP2B3 inhibition. In addition, knockdown of ATP2B3, NRF2, and P62 and overexpression of KEAP1 significantly down-regulated erastin\u2013induced high expression of the HO-1 protein, while HO-1 overexpression reversed the alleviating effects of ATP2B3 inhibition on the erastin\u2013induced decrease in cell viability (p &lt; 0.01) and increase in ROS production (p &lt; 0.01) in HT-22 cells. Taken together, ATP2B3 inhibition mediates the alleviation of erastin\u2013induced ferroptosis in HT-22 cells through the P62\u2013KEAP1\u2013NRF2\u2013HO-1 pathway.<\/jats:p>","DOI":"10.3390\/ijms24119199","type":"journal-article","created":{"date-parts":[[2023,5,25]],"date-time":"2023-05-25T02:58:48Z","timestamp":1684983528000},"page":"9199","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["ATP2B3 Inhibition Alleviates Erastin\u2013Induced Ferroptosis in HT-22 Cells through the P62\u2013KEAP1\u2013NRF2\u2013HO-1 Pathway"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8620-4239","authenticated-orcid":false,"given":"Shihui","family":"Guo","sequence":"first","affiliation":[{"name":"Key Laboratory of Animal Physiology and Biochemistry, Ministry of Agriculture and Rural Affairs, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing 210095, 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