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KMID : 1001920220650020236
Journal of Korean Neurosurgical Society
2022 Volume.65 No. 2 p.236 ~ p.244
Bioinformatics Analysis of Autophagy and Mitophagy Markers Associated with Delayed Cerebral Ischemia Following Subarachnoid Hemorrhage
Youn Dong-Hyuk

Kim Bong-Jun
Hong Eun-Pyo
Jeon Jin-Pyeong
Abstract
Objective: To evaluate the interactions among differentially expressed autophagy and mitophagy markers in subarachnoid hemorrhage (SAH) patients with delayed cerebral ischemia (DCI).

Methods: The expression data of autophagy and mitophagy-related makers in the cerebrospinal fluid (CSF) cells was analyzed by real-time reverse transcription-polymerase chain reaction and Western blotting. The markers included death-associated protein kinase (DAPK)-1, BCL2 interacting protein 3 like (BNIP3L), Bcl-1 antagonist X, phosphatase and tensin homolog-induced kinase (PINK), Unc-51 like autophagy activating kinase 1, nuclear dot protein 52, and p62. In silico functional analyses including gene ontology enrichment and the protein-protein interaction network were performed.

Results: A total of 56 SAH patients were included and 22 (38.6%) of them experienced DCI. The DCI patients had significantly increased mRNA levels of DAPK1, BNIP3L, and PINK1, and increased expression of BECN1 compared to the non-DCI patients. The most enriched biological process was the positive regulation of autophagy, followed by the response to mitochondrial depolarization. The molecular functions ubiquitin-like protein ligase binding and ubiquitin-protein ligase binding were enriched. In the cluster of cellular components, Lewy bodies and the phagophore assembly site were enriched. BECN1 was the most connected gene among the differentially expressed markers related to autophagy and mitophagy in the development of DCI.

Conclusion: Our study may provide novel insight into mitochondrial dysfunction in DCI pathogenesis.
KEYWORD
Subarachnoid hemorrhage, Autophagy, Brain ischemia, Cerebrospinal fluid, Bioinformatics
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