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Endoplasmic reticulum (ER) stress is reported to be involved in the development of I\/R injury. There is evidence that PERK exerts beneficial roles in alleviating ER stress. Here, we investigated whether upregulation of PERK improved cardiomyocytes injury induced by I\/R. Specific siRNAs or adenovirus vectors were incubated with isolated neonatal cardiomyocytes (NCMs) to regulate expression levels of target genes including PERK, Nrf2, and HO\u20101. Afterwards, hypoxia and subsequent reoxygenation (H\/R) administration was performed as the in vitro model of I\/R injury. MTT assay showed that H\/R intervention decreased the viability of cells, yet PERK overexpression increased the cellular proliferative rate. Moreover, the upregulation of Nrf2 or HO\u20101 elevated the growth rate of cells, while gene silencing of Nrf2 or HO\u20101 reduced the viability of NCMs treated with PERK\u2010rAAV9. In addition, we observed that the apoptotic index of cells with H\/R stimulation was reduced when NCMs were pretreated with PERK\u2010rAAV9, Nrf2\u2010rAAV9, or HO\u20101\u2010rAAV9. After cells were incubated with Nrf2\u2010siRNA or HO\u20101\u2010siRNA, the upregulation of PERK had no roles in affecting the apoptosis rate of NCMs damaged by H\/R. Then, our findings indicated that there was a level decrease of GRP78, CRT, CHOP, and Caspase\u201012 in NCMs of the PERK\u2010rAAV9 group compared to that of the H\/R group. Both Nrf2 overexpression and HO\u20101 upregulation reduced the expression of ER stress\u2010related proapoptotic factors, yet the expression suppression of Nrf2 and HO\u20101 increased levels of GRP78, CRT, CHOP, and Caspase\u201012 in NCMs treated with PERK\u2010rAAV9. Taken together, our results suggested that the effects of PERK against H\/R injury might be attributed to the upregulation of Nrf2\/HO\u20101 cascade, followed by the inhibition of ER stress\u2010related apoptotic pathway.<\/jats:p>","DOI":"10.1155\/2020\/6458060","type":"journal-article","created":{"date-parts":[[2020,3,26]],"date-time":"2020-03-26T23:32:44Z","timestamp":1585265564000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["PERK Overexpression\u2010Mediated Nrf2\/HO\u20101 Pathway Alleviates Hypoxia\/Reoxygenation\u2010Induced Injury in Neonatal Murine Cardiomyocytes via Improving Endoplasmic Reticulum 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