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: Xue Sun, Jun Jin, Ji-Gang Zhang, Lin Qi, Frank Karl Braun, Xing-Ding Zhang, Feng Xu
• Journal: Acta biochimica et biophysica Sinica (Acta Biochim Biophys Sin (Shanghai)) Vol. 46 Issue 9 Pg. 774-81 (Sep 2014) ISSN: 1745-7270 [Electronic] China
• PMID: 25079679 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: © The Author 2014. Published by ABBS Editorial Office in association with Oxford University Press on behalf of the Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences.

Chemical References

• ASIC1 protein, human
• Acid Sensing Ion Channels
• Anti-Inflammatory Agents, Non-Steroidal
• DNA Primers
• Ibuprofen

Topics

• Acid Sensing Ion Channels (metabolism)
• Anti-Inflammatory Agents, Non-Steroidal (pharmacology)
• Base Sequence
• DNA Primers
• Humans
• Ibuprofen (pharmacology)
• Intervertebral Disc (drug effects, metabolism)
• Polymerase Chain Reaction