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Protein kinase R\u2010like ER kinase (PERK)\/eukaryotic initiation factor 2 alpha (eIF2<jats:italic>\u03b1<\/jats:italic>) is an important factor along the main pathways for endoplasmic reticulum (ER) stress\u2010mediated apoptosis. In this study, we investigated the effects of eIF2<jats:italic>\u03b1<\/jats:italic> phosphorylation on hepatocyte apoptosis and the ER stress mechanisms in acute liver injury. <jats:italic>Methods<\/jats:italic>. eIF2<jats:italic>\u03b1<\/jats:italic> phosphorylation and apoptosis under ER stress were monitored and measured in male BALB\/c mice with acute liver injury and human hepatocyte line LO2 cells. <jats:italic>Results<\/jats:italic>. Carbon tetrachloride (CCl<jats:sub>4<\/jats:sub>) administration triggered ER stress and hepatocyte apoptosis, as well as eIF2<jats:italic>\u03b1<\/jats:italic> phosphorylation in mice. Inhibition of eIF2<jats:italic>\u03b1<\/jats:italic> dephosphorylation, as the pretreatment with 4\u2010phenylbutyric acid (chemical chaperone, ER stress inhibitor), mitigated CCl<jats:sub>4<\/jats:sub>\u2010induced intrahepatic ER stress, apoptosis, and liver injury. In an ER stress model of LO2 cells induced by thapsigargin (disrupting ER calcium balance), inhibition of eIF2<jats:italic>\u03b1<\/jats:italic> dephosphorylation reduced ER stress and apoptosis, while PERK knockdown reduced eIF2<jats:italic>\u03b1<\/jats:italic> phosphorylation and exacerbated ER stress and apoptosis. <jats:italic>Conclusions<\/jats:italic>. eIF2<jats:italic>\u03b1<\/jats:italic> phosphorylation is one of the mechanisms employed by ER stress for restoring cellular homeostasis. Inhibition of eIF2<jats:italic>\u03b1<\/jats:italic> dephosphorylation mitigates hepatocyte apoptosis by alleviating ER stress in acute liver injuries.<\/jats:p>","DOI":"10.1155\/2020\/2626090","type":"journal-article","created":{"date-parts":[[2020,6,5]],"date-time":"2020-06-05T23:35:02Z","timestamp":1591400102000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Inhibition of eIF2<i>\u03b1<\/i> Dephosphorylation Protects Hepatocytes from Apoptosis by Alleviating ER Stress in Acute Liver 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