title: Acid-sensing ion channels activation and hypoxia upregulate Homer1a expression.
abstract: 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 (ASICs) 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 (ERK1/2) and Akt activity, and ASIC1a-mediated calcium influx whereas hypoxia depended only on ERK1/2 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.
  
  
  CONCLUSIONS
  Homer1a might act as an activity-dependent regulator responding to extracellular stimuli during cerebral ischemia.
authors.affiliation: Department of Neurology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University, Shanghai, China.
authors.forename: Jing-Jing
authors.initials: JJ
authors.lastname: Su
authors.forename: Hui
authors.initials: H
authors.lastname: Pan
authors.forename: Hou-Guang
authors.initials: HG
authors.lastname: Zhou
authors.forename: Yu-Ping
authors.initials: YP
authors.lastname: Tang
authors.forename: Qiang
authors.initials: Q
authors.lastname: Dong
authors.forename: Jian-Ren
authors.initials: JR
authors.lastname: Liu
mesh_terms: D018750:6-Cyano-7-nitroquinoxaline-2,3-dione / Q000494:pharmacology; D062646:Acid Sensing Ion Channel Blockers / Q000494:pharmacology; D062565:Acid Sensing Ion Channels / Q000378:metabolism*; D000584:Amiloride / Q000494:pharmacology; D000818:Animals; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D002470:Cell Survival; D002478:Cells, Cultured; D004195:Disease Models, Animal; D016291:Dizocilpine Maleate / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D000072233:Homer Scaffolding Proteins; D000860:Hypoxia / Q000378:metabolism / Q000473:pathology; D020244:Infarction, Middle Cerebral Artery / Q000378:metabolism* / Q000503:physiopathology; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D010455:Peptides / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects; D013111:Spider Venoms / Q000494:pharmacology; D013997:Time Factors; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology*
chemical_list: D062646:Acid Sensing Ion Channel Blockers; D062565:Acid Sensing Ion Channels; D002352:Carrier Proteins; D018691:Excitatory Amino Acid Antagonists; D000072233:Homer Scaffolding Proteins; C413209:PcTX1 protein, Psalmopoeus cambridgei; D010455:Peptides; D013111:Spider Venoms; D016291:Dizocilpine Maleate; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; D000584:Amiloride
keywords: Acid-sensing ion channels; Akt; ERK1/2; Homer1a; Hypoxia