The Protective Mechanism of Protein Kinase R to Inhibit Neuronal Ferroptosis in Cerebral Injury from Subarachnoid Hemorrhage

Overview

Journal Brain Behav

Specialty Psychology

Date 2022 Jul 27

PMID 35894766

Authors

Jianwei Lei

Shuxin Song

Zhihua Chen

Sihong Shu

Qiang Liu

Wei Hu

Affiliations

Soon will be listed here.

Abstract

Purpose: To investigate the role and mechanism of protein kinase R (PKR) in subarachnoid hemorrhage (SAH)-mediated ferroptosis.

Methods: A rat SAH model was constructed and treated with PKR inhibitor C16 to observe SAH and neurological impairment in rats and to detect malonaldehyde (MDA), iron ions content, ferritin heavy polypeptide 1 (FTH1) and glutathione peroxidase 4 (GPX4), and other related ferroptosis indicators in brain tissue. RNA sequencing analysis was used to investigate the mechanism of PKR, affecting the ferroptosis network of SAH.

Results: SAH caused severe fundic hemorrhage, neurological impairment, MDA and iron ion accumulation, and significant decrease in GPX4 and FTH1 levels in rats. C16 treatment significantly improved the above signs caused by SAH. By RNA-seq analysis, brain tissue of SAH-treated rats with SAH and C16 differentially expressed mRNA target genes enriched in stress response and organic developmental signaling pathways.

Conclusion: Inhibition of PKR may improve cerebral injury after SAH by inhibiting ferroptosis, and RNA sequencing staged its mechanism of action may be related to the stress response.

Citing Articles

Pharmacological Inhibition of Ferroptosis as a Therapeutic Target for Neurodegenerative Diseases and Strokes.

Wang Y, Wu S, Li Q, Sun H, Wang H Adv Sci (Weinh). 2023; 10(24):e2300325.

PMID: 37341302 PMC: 10460905. DOI: 10.1002/advs.202300325.

The protective mechanism of protein kinase R to inhibit neuronal ferroptosis in cerebral injury from subarachnoid hemorrhage.

Lei J, Song S, Chen Z, Shu S, Liu Q, Hu W Brain Behav. 2022; 12(8):e2722.

PMID: 35894766 PMC: 9392539. DOI: 10.1002/brb3.2722.

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Lei J, Song S, Chen Z, Shu S, Liu Q, Hu W . The protective mechanism of protein kinase R to inhibit neuronal ferroptosis in cerebral injury from subarachnoid hemorrhage. Brain Behav. 2022; 12(8):e2722. PMC: 9392539. DOI: 10.1002/brb3.2722. View