title: Down-regulation of ASICs current and the calcium transients by disrupting PICK1 protects primary cultured mouse cortical neurons from OGD-Rep insults.
abstract: Acid sensing ion channels (ASICs), activated by lowering extracellular pH, play an important role in normal synaptic transmission in brain and in the pathology of brain ischemia. ASICs activation involving in glutamate receptor-independent ischemic brain injury has been generally accepted, and PICK1 is recently shown to be one of partner proteins interacting with ASICs through its PDZ domain. Here we showed that ASICs and PICK1 played key roles in OGD-Rep process. In wild-type cultured cortical neurons, not only the amplitude of ASICs current and the calcium transients induced by acidosis were both increased after OGD-Rep, but also the total protein levels of ASIC1 and ASIC2a were up-regulated progressively after ischemia insults, indicating that ASICs play a vital role in neuronal ischemia. However, these activities were reversed with PICK1-knockout after OGD-Rep, accompanied with the dramatically down-regulating the protein abundances of ASIC1 and ASIC2a, which suggested the neuroprotection activity in brain ischemia by PICK1-knockout. These results indicate that knocking-out PICK1 gene casts the neuroprotection effect by reducing ASICs current and the calcium transients in OGD-Rep neuronal cells, which will offer a promising strategy in the therapy of brain ischemia.
authors.affiliation: Department of Pharmacology, Xiangyang Central Hospital, Affiliated Hospital of Hubei University of Arts and Science Xiangyang 441021, China.
authors.forename: Jin
authors.initials: J
authors.lastname: Cheng
authors.affiliation: Shanghan Teaching and Research Section, Clinical College of Chinese Medicine, Huben University of Traditional Chinese Medicine Wuhan 430061, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Department of Gynaecology and Obstetrics, Xiangyang Central Hospital, Affiliated Hospital of Hubei University of Arts and Science Xiangyang 441021, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Xing
authors.affiliation: Clinical Lboratory, Xiangyang Central Hospital, Affiliated Hospital of Hubei University of Arts and Science Xiangyang 441021, China.
authors.forename: Hua
authors.initials: H
authors.lastname: Jiang
authors.affiliation: Department of Anesthesiology, Xiangyang Central Hospital, Affiliated Hospital of Hubei University of Arts and Science Xiangyang 441021, China.
authors.forename: Xihong
authors.initials: X
authors.lastname: Ye
mesh_terms: D062565:Acid Sensing Ion Channels / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D018797:Cell Cycle Proteins; D015687:Cell Hypoxia / Q000235:genetics; D002540:Cerebral Cortex / Q000166:cytology / Q000378:metabolism*; D015536:Down-Regulation; D005947:Glucose / Q000172:deficiency; D051379:Mice; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D000066829:Neuroprotection / Q000235:genetics*; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D062565:Acid Sensing Ion Channels; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D009687:Nuclear Proteins; C091822:Prkcabp protein, mouse; D005947:Glucose; D002118:Calcium
keywords: ASICs; OGD-Rep; PICK1; brain ischemia; calcium transients; neuroprotection