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.

CONCLUSION:

Homer1a might act as an activity-dependent regulator responding to extracellular stimuli during cerebral ischemia.

• Authors: Jing-Jing Su, Hui Pan, Hou-Guang Zhou, Yu-Ping Tang, Qiang Dong, Jian-Ren Liu
• Journal: CNS neuroscience & therapeutics (CNS Neurosci Ther) Vol. 20 Issue 3 Pg. 264-74 (Mar 2014) ISSN: 1755-5949 [Electronic] England
• PMID: 24433527 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2014 John Wiley & Sons Ltd.

Chemical References

• Acid Sensing Ion Channel Blockers
• Acid Sensing Ion Channels
• Carrier Proteins
• Excitatory Amino Acid Antagonists
• Homer Scaffolding Proteins
• PcTX1 protein, Psalmopoeus cambridgei
• Peptides
• Spider Venoms
• Dizocilpine Maleate
• 6-Cyano-7-nitroquinoxaline-2,3-dione
• Amiloride

Topics

• 6-Cyano-7-nitroquinoxaline-2,3-dione (pharmacology)
• Acid Sensing Ion Channel Blockers (pharmacology)
• Acid Sensing Ion Channels (metabolism)
• Amiloride (pharmacology)
• Animals
• Carrier Proteins (genetics, metabolism)
• Cell Survival
• Cells, Cultured
• Disease Models, Animal
• Dizocilpine Maleate (pharmacology)
• Excitatory Amino Acid Antagonists (pharmacology)
• Homer Scaffolding Proteins
• Hypoxia (metabolism, pathology)
• Infarction, Middle Cerebral Artery (metabolism, physiopathology)
• Neurons (drug effects, metabolism)
• Peptides (pharmacology)
• Rats
• Rats, Sprague-Dawley
• Signal Transduction (drug effects)
• Spider Venoms (pharmacology)
• Time Factors
• Up-Regulation (drug effects, physiology)