Noise-induced up-regulation of NTPDase3 expression in the rat cochlea: Implications for auditory transmission and cochlear protection.
Noise-induced up-regulation of NTPDase3 expression in the rat cochlea: Implications for auditory transmission and cochlear protection.
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噪声诱导的大鼠耳蜗中 NTPDase3 表达上调：对听觉传输和耳蜗保护的影响。
DOI：
10.1016/j.brainres.2006.05.094
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发表时间：
2006
期刊：
影响因子：
2.9
通讯作者：
Housley,GaryD
中科院分区：
文献类型：
--
作者：
Vlajkovic,SrdjanM;Vinayagamoorthy,Aravinthan;Thorne,PeterR;Robson,SimonC;Wang,CarolJH;Housley,GaryD
噪音或缺氧等刺激可诱导ATP释放到耳蜗液腔中。在纳摩尔浓度下，ATP影响神经传递和声传导的电化学调节。在较高浓度下，ATP可能对特定的p2x7受体亚基产生细胞毒性，从而参与噪声性耳蜗损伤的病理生理过程。外核苷三磷酸二磷酸水解酶（e - ntpases）是调节细胞外核苷酸浓度和耳蜗P2受体信号的关键。在这里，我们表征了NTPDase3外核苷酸酶（优先水解ATP而不是ADP）在耳蜗组织中的分布，并研究了噪声暴露对NTPDase3表达的影响。在螺旋神经节的初级传入神经元中有显著的NTPDase3免疫反应性，从远端神经突延伸到内外毛细胞下的突触，提示与听觉神经传递有关。耳蜗外壁和耳蜗隔壁上皮细胞的免疫标记也很明显。半定量免疫组织化学显示，在诱导暂时阈值移位的声强下，内外部毛细胞突触区域的NTPDase3免疫标记增加。结果表明，NTPDase3在调节主要与听觉神经传递相关的ATP信号中发挥作用，以及噪声诱导耳蜗中该外核苷酸酶上调的潜在神经保护性质。
Stimuli such as noise or hypoxia can induce a release of ATP into the cochlear fluid spaces. At nanomolar concentrations, ATP affects neurotransmission and electrochemical regulation of sound transduction. At higher concentrations, ATP may exert cytotoxicity acting on specific P2X7receptor subunits, thus contributing to the pathophysiology of noise-induced cochlear injury. Ectonucleoside triphosphate diphosphohydrolases (E-NTPDases) are pivotal to regulation of extracellular nucleotide concentrations and therefore P2 receptor signaling in the cochlea. Here, we characterize the distribution of NTPDase3 ectonucleotidase (preferentially hydrolyzes ATP over ADP) in cochlear tissues and investigate the effect of noise exposure on NTPDase3 expression. Marked NTPDase3 immunoreactivity in the primary afferent neurones of the spiral ganglion, extending in the distal neurite processes to the synapses beneath the inner and outer hair cells, suggests involvement in auditory neurotransmission. Immunolabeling in the lateral wall and epithelial cells lining the cochlear partition was also evident. Semi-quantitative immunohistochemistry revealed increased NTPDase3 immunolabeling in the synaptic regions of the inner and outer hair cells at sound intensities that induce temporary threshold shift. The results suggest a role for NTPDase3 in regulating ATP signaling associated primarily with auditory neurotransmission, and the potential neuroprotective nature of noise-induced up-regulation of this ectonucleotidase in the cochlea.