Open AccessAcid‐sensing Ion Channels Activation and Hypoxia Upregulate Homer1a Expression
Author(s) -
Su JingJing,
Pan Hui,
Zhou HouGuang,
Tang YuPing,
Dong Qiang,
Liu JianRen
Publication year - 2014
Publication title -
cns neuroscience and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.403
H-Index - 69
eISSN - 1755-5949
pISSN - 1755-5930
DOI - 10.1111/cns.12206
Subject(s) - downregulation and upregulation , hypoxia (environmental) , ion channel , chemistry , microbiology and biotechnology , neuroscience , biology , biochemistry , gene , oxygen , receptor , organic chemistry
Summary Background Recent studies have indicated that dynamic alterations in the structure of postsynaptic density ( PSD ) are involved in the pathogenesis of many central nervous system disorders, including ischemic stroke. Homer is the newly identified scaffolding protein located at PSD and regulates synaptic function. Homer1a, an immediate early gene, has been shown to be induced by several stimulations, such as glutamate, brain‐derived neurotrophic factor, and trauma. However, whether acidosis mediated by acid‐sensing ion channels ( ASIC s) and hypoxia during cerebral ischemia can change Homer1a expression remains to be determined. Results We investigated that acidosis and hypoxia selectively and rapidly upregulated Homer1a expression, but not Homer1b/c in cultured cortical neurons. We also found that Homer1a exhibited induction expression in brain cortex of the middle cerebral artery occlusion ( MCAO ) rats. Additionally, acid‐evoked Homer1a mRNA induction depended on extracellular signal‐regulated kinase1/2 ( ERK 1/2) and Akt activity, and ASIC1a ‐mediated calcium influx whereas hypoxia depended only on ERK 1/2 activity. Also, we demonstrated that continuous acidosis and hypoxia resulted in pronounced cell injury and Homer1a knockdown with small interfering RNA aggravated this damage induced by 3 h acid and hypoxia incubation in neuro‐2a cells. Conclusion Homer1a might act as an activity‐dependent regulator responding to extracellular stimuli during cerebral ischemia.