Possible mechanisms of the PERK pathway on neuronal apoptosis in a rat model of surgical brain injury

Mu-Yao Wu; Fan Gao; Jia-Feng Tang; Jin-Chao Shen; Rong Gao; Bao-Qi Dang; Gang Chen

Possible mechanisms of the PERK pathway on neuronal apoptosis in a rat model of surgical brain injury

Am J Transl Res. 2021 Feb 15;13(2):732-742. eCollection 2021.

Authors

Mu-Yao Wu¹, Fan Gao¹, Jia-Feng Tang¹, Jin-Chao Shen², Rong Gao³, Bao-Qi Dang¹, Gang Chen⁴

Affiliations

¹ Department of Rehabilitation, Zhangjiagang TCM Hospital Affiliated to Nanjing University of Chinese Medicine Suzhou, China.
² Anesthesiology Department, Zhangjiagang TCM Hospital Affiliated to Nanjing University of Chinese Medicine Suzhou, China.
³ Department of Neurosurgery, Zhangjiagang TCM Hospital Affiliated to Nanjing University of Chinese Medicine Suzhou, China.
⁴ Department of Neurosurgery and Brain and Nerve Research Laboratory, The First Affiliated Hospital of Soochow University Suzhou, China.

PMID: 33594322
PMCID: PMC7868842

Abstract

Protein kinase R-like endoplasmic reticulum kinase (PERK) is an important transmembrane protein in the endoplasmic reticulum (ER). PERK signaling has a critical function in neuronal apoptosis. This work aimed to assess PERK signaling for its function in surgical brain injury (SBI) and to explore the underlying mechanisms. Totally 120 male Sprague Dawley (SD) rats were assessed in an SBI model. The effects of the PERK inhibitor GSK2606414 were examined by Western-blot, immunofluorescent staining, TUNEL staining, fluoro-jade C (FJC) staining and neurological assays in rats with SBI. In this study, p-PERK and p-eIF2α protein amounts were increased upon SBI establishment, peaking at 24 h. Meanwhile, administration of GSK2606414 reversed these effects and prevented neuronal apoptosis. The PERK pathway has a significant function in neuronal apoptosis, and its suppression after SBI promotes the alleviation of brain injury. This suggests that targeting the PERK signaling pathway may represent an efficient therapeutic option for improving prognosis in SBI patients.

Keywords: ER stress; PERK; SBI; UPR; apoptosis; eIF2α.