Sun Xue, Jin Jun, Zhang Ji-Gang, Qi Lin, Braun Frank Karl, Zhang Xing-Ding, Xu Feng
Emergency Department, First Affiliated Hospital of Soochow University, Suzhou 215006, China.
Laboratory of Molecular Neuro-Oncology, Texas Children's Cancer Center, Houston 77030, USA.
Acta Biochim Biophys Sin (Shanghai). 2014 Sep;46(9):774-81. doi: 10.1093/abbs/gmu067. Epub 2014 Jul 30.
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.
非甾体抗炎药（NSAIDs）通常通过抑制环氧化酶（COX）来治疗炎症和疼痛。越来越多的证据表明，NSAIDs还有其他不依赖COX的靶点，包括酸敏感离子通道（ASICs）1a和3。然而，ASICs的详细功能和机制仍 largely难以捉摸。在本研究中，我们调查了NSAIDs对人椎间盘髓核细胞中ASICs的影响。从40例患者的突出椎间盘组织中分离并培养髓核细胞。通过分析ASIC抑制后的质子门控电流，表明ASIC1a和ASIC3在这些细胞中表达且具有功能。我们进一步研究了布洛芬（一种COX抑制剂）、蛛毒素-1（PcTX1，一种对同源ASIC1a特异的狼蛛毒素）和氨氯吡脒（ASICs所属的上皮钠通道ENaC/DEG家族的经典抑制剂）的神经保护能力。在缺血性啮齿动物模型中，含PcTX1的毒液已被证明在神经保护特性方面与氨氯吡脒相当。综上所述，我们的数据表明，氨氯吡脒、PcTX1和布洛芬降低了ASIC蛋白表达，从而对ASIC抑制介导的细胞损伤发挥保护作用。
