title: Expression of acid-sensing ion channels in nucleus pulposus cells of the human intervertebral disk is regulated by non-steroid anti-inflammatory drugs.
abstract: Non-steroid anti-inflammatory drugs (NSAIDs) are generally used in the treatment of inflammation and pain through cyclooxygenase (COX) inhibition. Mounting evidence has indicated additional COX-independent targets for NSAIDs including acid-sensing ion channels (ASICs) 1a and 3. However, detailed function and mechanism of ASICs still remain largely elusive. In this study, the impact of NSAIDs on ASICs in nucleus pulposus cells of the human intervertebral disk was investigated. Nucleus pulposus cells were isolated and cultured from protruded disk tissues of 40 patients. It was shown that ASIC1a and ASIC3 were expressed and functional in these cells by analyzing proton-gated currents after ASIC inhibition. We further investigated the neuroprotective capacity of ibuprofen (a COX inhibitor), psalmotoxin-1 (PcTX1, a tarantula toxin specific for homomeric ASIC1a), and amiloride (a classic inhibitor of the epithelial sodium channel ENaC/DEG family to which ASICs belong). PcTX1-containing venom has been shown to be comparable with amiloride in its neuroprotective features in rodent models of ischemia. Taken together, our data showed that amiloride, PcTX1, and ibuprofen decreased ASIC protein expression and thereby exerted protective effects from ASIC inhibition-mediated cell damage.
authors: Emergency Department, First Affiliated Hospital of Soochow University, Suzhou 215006, China.
authors: Xue
authors: X
authors: Sun
authors: Emergency Department, First Affiliated Hospital of Soochow University, Suzhou 215006, China.
authors: Jun
authors: J
authors: Jin
authors: Emergency Department, First Affiliated Hospital of Soochow University, Suzhou 215006, China.
authors: Ji-Gang
authors: JG
authors: Zhang
authors: Laboratory of Molecular Neuro-Oncology, Texas Children's Cancer Center, Houston 77030, USA.
authors: Lin
authors: L
authors: Qi
authors: Department of Lymphoma & Myeloma, The University of Texas M.D. Anderson Cancer Center, Houston 77054, USA.
authors: Frank Karl
authors: FK
authors: Braun
authors: Department of Lymphoma & Myeloma, The University of Texas M.D. Anderson Cancer Center, Houston 77054, USA Cyrus Tang Hematology Center, Soochow University, Suzhou 215123, China xufengsafyy@gmail.com ading5@hotmail.com.
authors: Xing-Ding
authors: XD
authors: Zhang
authors: Emergency Department, First Affiliated Hospital of Soochow University, Suzhou 215006, China xufengsafyy@gmail.com ading5@hotmail.com.
authors: Feng
authors: F
authors: Xu
mesh_terms: D062565:Acid Sensing Ion Channels / Q000378:metabolism*; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D001483:Base Sequence; D017931:DNA Primers; D006801:Humans; D007052:Ibuprofen / Q000494:pharmacology; D007403:Intervertebral Disc / Q000187:drug effects* / Q000378:metabolism; D016133:Polymerase Chain Reaction
chemical_list: C568266:ASIC1 protein, human; D062565:Acid Sensing Ion Channels; D000894:Anti-Inflammatory Agents, Non-Steroidal; D017931:DNA Primers; D007052:Ibuprofen
keywords: acid-sensing ion channel (ASIC); ibuprofen; intervertebral disk; non-steroid anti-inflammatory drug (NSAID); nucleus pulposus cells