Yang Yuan - Department of Anesthesiology, Qingdao Municipal Hospital, Qingdao, Shandong, China
Hongchen Tan - Malvern College Qingdao, Qingdao, Shandong, China
Huailong Chen - Department of Anesthesiology, Qingdao Eight People’s Hospital, Qingdao, Shandong, China
Jiawen Zhang - Department of Anesthesiology, Qingdao Clinical College Affiliated to Nanjing Medical University, Qingdao, Shandong, China
Fei Shi - Department of Anesthesiology, Qingdao Municipal Hospital, Qingdao, Shandong, China
Mingshan Wang - Department of Anesthesiology, Qingdao Municipal Hospital, Qingdao, Shandong, China
Gaofeng Zhang - Department of Anesthesiology, Qingdao Municipal Hospital, Qingdao, Shandong, China
Haipeng Wang - Department of Anesthesiology, Weifang No.۲ People’s Hospital, Weifang, Shandong, China
Rui Dong - Department of Anesthesiology, Qingdao Municipal Hospital, Qingdao, Shandong, China

Objective(s): Cerebral ischemia/reperfusion (I/R) injury inevitably aggravates the initial cerebral tissue damage following a stroke. Peroxiredoxin ۱ (Prdx۱) is a representative protein of the endogenous antioxidant enzyme family that regulates several reactive oxygen species (ROS)-dependent signaling pathways, whereas the JNK/caspase-۳ proapoptotic pathway has a prominent role during cerebral I/R injury. This study aimed to examine the potential mechanism of Prdx۱ in Neuro ۲A (N۲a) cells following oxygen–glucose deprivation and reoxygenation (OGD/R) injury. Materials and Methods: N۲a cells were exposed to OGD/R to simulate cerebral I/R injury. Prdx۱ siRNA transfection and the JNK inhibitor (SP۶۰۰۱۲۵) were used to interfere with their relative expressions. CCK-۸ assay, flow cytometry, and lactate dehydrogenase (LDH) assay were employed to determine the viability and apoptosis of N۲a cells. The intracellular ROS content was assessed using ROS Assay Kit. Real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR) and western blot analyses were conducted to detect the expression levels of Prdx۱, JNK, phosphorylated JNK (p-JNK), and cleaved caspase-۳. Results: Firstly, Prdx۱, p-JNK, and cleaved caspase-۳ expression were significantly induced in OGD/R-exposed N۲a cells. Secondly, the knockdown of Prdx۱ inhibited cell viability and increased apoptosis rate, expression of p-JNK, and cleaved caspase-۳ expression. Thirdly, SP۶۰۰۱۲۵ inhibited the JNK/caspase-۳ signaling pathway and mitigated cell injury following OGD/R. Finally, SP۶۰۰۱۲۵ partially reversed Prdx۱ down-regulation-mediated cleaved caspase-۳ activation and OGD/R damage in N۲a cells. Conclusion: Prdx۱ alleviates the injury to N۲a cells induced by OGD/R via suppressing JNK/caspase-۳ pathway, showing promise as a potential therapeutic for cerebral I/R injury.

Caspase-۳, Cell Hypoxia, c-Jun N-terminal kinase, Mice, Neuroblastoma, Peroxiredoxin ۱, Reperfusion injury