期刊
NEUROSCIENCE LETTERS
卷 758, 期 -, 页码 -出版社
ELSEVIER IRELAND LTD
DOI: 10.1016/j.neulet.2021.136004
关键词
GADD34; Plasma exosomes; Ischemic stroke; Biomarker
资金
- National Natural Science Foundation of China [81971231]
- Xingliao Yingcai Project Foundation of Liaoning Province [XLYC1907178]
- Scientific Research Project from the Educational Department of Liaoning Province [JYTQN2020011]
GADD34 is upregulated in the cortex of ischemic rats and contributes to brain injury; treatment with a GADD34 inhibitor improves neuronal damage post-ischemia, suggesting it as a potential therapeutic target for ischemic stroke; the expression of GADD34 is increased in plasma exosomes of cerebral ischemic rats, indicating its potential as a biomarker.
Growth arrest and DNA damage-inducible protein 34 (GADD34), one of the key effectors of negative feedback loops, is induced by stress and subsequently attempts to restore homeostasis. It plays a critical role in response to DNA damage and endoplasmic reticulum stress. GADD34 has opposing effects on different stimulus-induced cell apoptosis events in many nervous system diseases, but its role in ischemic stroke is unclear. In this study, we evaluated the role of GADD34 and its distribution in a rat cerebral ischemic model. The results showed that GADD34 was increased in the cortex and contributed to brain injury in ischemic rats. Furthermore, treatment with a GADD34 inhibitor reduced the infarct volume, improved functional outcomes, and inhibited neuronal apoptosis in the cortical penumbra after ischemia. The role of GADD34 in ischemic stroke was associated with the dephosphorylation of eukaryotic translation initiation factor 2 alpha (eIF2 alpha) and phosphorylation of p53. In addition, the GADD34 level was increased in plasma exosomes of cerebral ischemic rats. These findings indicate that GADD34 could be a potential therapeutic target and biomarker for ischemic stroke.
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