Oxygen–Glucose Deprivation Increases NR4A1 Expression and Promotes Its Extranuclear Translocation in Mouse Astrocytes

Autor: Kengo Moriyama, Asako Horino, Kuniko Kohyama, Yasumasa Nishito, Tomohiro Morio, Hiroshi Sakuma
Jazyk: angličtina
Rok vydání: 2024
Předmět:
Zdroj: Brain Sciences, Vol 14, Iss 3, p 244 (2024)
Druh dokumentu: article
ISSN: 2076-3425
DOI: 10.3390/brainsci14030244
Popis: Hypoxic–ischemic brain injury induces metabolic dysfunction that ultimately leads to neuronal cell death. Astrocytes, a type of glial cell, play a key role in brain metabolism; however, their response to hypoxic–ischemic brain injury is not fully understood. Microglia were removed from murine primary mixed glial cultures to enrich astrocytes. Next, we explored genes whose expression is altered following oxygen–glucose deprivation using a microarray. Microarray analysis revealed that the expression of Nr4a1 and Nr4a3 is markedly increased in astrocyte-enriched cultures after 15 h of oxygen–glucose deprivation. The expression of both Nr4a1 and Nr4a3 was regulated by HIF-1α. At the protein level, NR4A1 was translocated from the nucleus to the cytoplasm following oxygen–glucose deprivation and co-localized with mitochondria in apoptotic cells; however, its localization was restored to the nucleus after reoxygenation. Oxygen–glucose deprivation causes an increase in NR4A1 mRNA in astrocytes as well as its nuclear to cytoplasmic transfer. Furthermore, reoxygenation enhances NR4A1 transcription and promotes its nuclear translocation.
Databáze: Directory of Open Access Journals
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