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

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...

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Published in:Brain and behavior 2022-08, Vol.12 (8), p.e2722-n/a
Main Authors: Lei, Jianwei, Song, Shuxin, Chen, Zhihua, Shu, Sihong, Liu, Qiang, Hu, Wei
Format: Article
Language:English
Subjects:
Antibodies
Apoptosis
Carotid arteries
Ferroptosis
Genomes
Hemoglobin
Hemorrhage
Iron
Kinases
Original
Polymerase chain reaction
protein kinase R
Proteins
RNA sequencing
subarachnoid hemorrhage
Veins & arteries
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Summary: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. Graphical Inhibition of PKR may significantly ameliorate SAH‐induced EBI by regulating iron death.
ISSN:2162-3279
2162-3279
DOI:10.1002/brb3.2722