Expression of acid-sensing ion channels in nucleus pulposus cells of the human intervertebral disk is regulated by non-steroid anti-inflammatory drugs

Xue Sun, Jun Jin, Ji Gang Zhang, Lin Qi, Frank Karl Braun, Xing Ding Zhang*, Feng Xu

*Corresponding author for this work

Research output: Contribution to journalArticle

9 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)774-781
Number of pages8
JournalActa biochimica et biophysica Sinica
Volume46
Issue number9
DOIs
StatePublished - Dec 26 2013

Keywords

  • Acid-sensing ion channel (ASIC)
  • Ibuprofen
  • Intervertebral disknucleus pulposus cells
  • Non-steroid anti-inflammatory drug (NSAID)

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry

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