ETS-domain containing protein (Elk1) suppression protects cortical neurons against oxygen-glucose deprivation injury

Journal Article · Mon Oct 15 04:00:00 EDT 2018 · Experimental Cell Research

DOI:https://doi.org/10.1016/J.YEXCR.2018.07.038· OSTI ID:23082575

Lu, Zhaofeng ^[1]; Miao, Zhuang ^[2]; Zhu, Jian ^[3]; Zhu, Gangyi ^[1]

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1. Department of Emergency, First Affiliated Hospital, Henan University of Science and Technology, Luoyang 471000 (China)
2. Department of Neurosurgery, China-Japan Union Hospital of Jilin University, Changchun 130033 (China)
3. Department of Neurosurgery, The First People's Hospital of Yancheng( The Fourth Affiliated Hospital of Nantong University), Yancheng 224006 (China)

Highlights: • Elk1 expression is up-regulated by OGD in the neurons. • Elk1 suppression inhibits neurons apoptosis induced by OGD. • Elk1 suppression restrains OGD-induced neurons cytotoxicity. • Elk1 suppression lessens MDA and SOD contents in neurons with OGD injury. • Elk1 suppression protects neurons against OGD injury via regulating Fra-1/Nrf2. ETS-domain containing protein (Elk1), which is a transcription factor, is reported to be closely related to the apoptosis of primary neurons and could be activated by hypoxia in human microvascular endothelial cells. In this study, we aimed to investigate the role of Elk1 in cortical neurons under oxygen-glucose deprivation (OGD) conditions. The OGD model of cortical neurons was established the anoxia/hypoglycemia-induced injury and the in vivo model was established by middle cerebral artery occlusion (MCAO). Elk1 mRNA and protein expression was significantly up-regulated in neurons exposed to OGD for 24 h, and mRNA expression was also markedly increased in cerebral cortex of rats with MCAO after 10 days. The knockdown of Elk1 in neurons without OGD obviously constrained Fra-1 and promoted Nrf2 expression. Also, Elk1 inhibition suppressed neuronal apoptosis, caspase-3 activity, LDH leakage, and MDA and SOD contents, while it increased cell viability in the neurons with OGD. The overexpression of Fra-1 showed a reverse effect on caspase-3 activity, cell viability and SOD contents in neurons under OGD conditions compared with Elk1 knockdown. Thus, Elk1 inhibition has a protective effect on neurons against OGD-induced injury.

• OSTI ID: 23082575
• Journal Information: Experimental Cell Research, Journal Name: Experimental Cell Research Journal Issue: 1 Vol. 371; ISSN 0014-4827; ISSN ECREAL
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
CEREBRAL ARTERIES
CEREBRAL CORTEX
GLUCOSE
MESSENGER-RNA
NERVE CELLS
RATS
TRANSCRIPTION FACTORS