title: Regulation of acid-sensing ion channel 1a function by tissue kallikrein may be through channel cleavage.
abstract: Recently, we have demonstrated that serine protease tissue kallikrein (TK) can protect cortical neurons against ischemia-acidosis/reperfusion-induced injury, and that this effect might be mediated by acid-sensing ion channels (ASICs). However, little is known about how TK regulates the function of ASICs. Here we provided evidence that the regulation of ASIC1a function by TK was probably correlated with its cleavage. High concentration of TK (3μM) partially cleaved the extracellular loop of ASIC1a, followed by a marked decrease of LDH release and an increase of cell survival at pH 6.2. Pretreatment with a protease inhibitor aprotinin inhibited the cleavage of ASIC1a and prevented functional regulation by TK. However, the cleavage of ASIC2a, which was not functionally modified by TK, was not observed. Therefore, we propose that the limited proteolysis of extracellular loop within ASIC1a might be one of the potential regulatory mechanisms of ASIC1a function by TK.
authors.affiliation: Department of Neurology, Huashan Hospital, Fudan University, Shanghai 200040, China. jjsubz@yahoo.com.cn
authors.forename: Jingjing
authors.initials: J
authors.lastname: Su
authors.forename: Yuping
authors.initials: Y
authors.lastname: Tang
authors.forename: Ling
authors.initials: L
authors.lastname: Liu
authors.forename: Houguang
authors.initials: H
authors.lastname: Zhou
authors.forename: Qiang
authors.initials: Q
authors.lastname: Dong
mesh_terms: D062565:Acid Sensing Ion Channels; D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism*; D002461:Cell Line, Transformed; D002470:Cell Survival / Q000187:drug effects; D000697:Central Nervous System Stimulants / Q000494:pharmacology; D003029:Coagulants / Q000494:pharmacology*; D062626:Degenerin Sodium Channels; D004305:Dose-Response Relationship, Drug; D053503:Epithelial Sodium Channels / Q000378:metabolism; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007610:Kallikreins / Q000494:pharmacology*; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D009419:Nerve Tissue Proteins / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D010852:Picrotoxin / Q000494:pharmacology; D015222:Sodium Channels / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D014162:Transfection / Q000379:methods
chemical_list: D062565:Acid Sensing Ion Channels; D000697:Central Nervous System Stimulants; D003029:Coagulants; D062626:Degenerin Sodium Channels; D053503:Epithelial Sodium Channels; D007610:Kallikreins; D007770:L-Lactate Dehydrogenase; D009419:Nerve Tissue Proteins; D010852:Picrotoxin; D015222:Sodium Channels; C568266:ASIC1 protein, human; C568267:ASIC1 protein, mouse; C568424:ASIC2 protein, human