Mitochondria toxin-induced acute cochlear cell death indicates cellular activity-correlated energy consumption
Mitochondria toxin-induced acute cochlear cell death indicates cellular activity-correlated energy consumption
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DOI：
10.1007/s00405-012-2267-1
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发表时间：
2013-09
影响因子：
2.6
通讯作者：
J. Zou;Ya Zhang;Weikai Zhang;D. Poe;Suoqiang Zhai;Shi-ming Yang;I. Pyykkö
中科院分区：
文献类型：
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作者：
J. Zou;Ya Zhang;Weikai Zhang;D. Poe;Suoqiang Zhai;Shi-ming Yang;I. Pyykkö
耳蜗内不同类型的细胞可能对代谢衰竭的病理变化有特定的贡献，这可能为开发新的内耳治疗策略提供线索。为了评估耳蜗代谢衰竭过程中与活性相关的细胞死亡，使用3-硝基丙酸对呼吸链进行不可逆抑制。体外观察耳蜗细胞对3-硝基丙酸的剂量反应。3-硝基丙酸灌胃豚鼠圆窗。通过末端转移酶在体内标记DNA链中的游离3'OH断裂和体外碘化丙啶核渗透来鉴定细胞死亡。结果表明，10 mM和100 mM的3-硝基丙酸分别在体外诱导23.6%和96.3%的细胞死亡。在豚鼠中，500mm 3-硝基丙酸引起前庭功能障碍和严重到深度的听力损失。对3-硝基丙酸处理最敏感的细胞包括纹边缘和中间细胞、雷氏膜上皮细胞和螺旋韧带纤维细胞（II型和V型）。中度敏感细胞为螺旋边缘中心区的卫星纤维细胞、耳蜗壳的骨细胞、毛细胞和螺旋神经节细胞。暴露后，螺旋神经节细胞的胞体和周围突的神经丝减少。这些结果可能与突发性感音神经性听力损失和有害物质暴露致听力损失的损伤机制有关。
The different cell types within the cochlea may have a specific contribution to the pathological changes during metabolism failure, which may provide clues for developing novel strategies for inner ear therapy. In order to evaluate activity-correlated cell death during metabolism failure in the cochlea, 3-nitropropionic acid was used to irreversibly inhibit the respiratory chain. Dose–response of the cochlear cells to 3-nitropropionic acid was analyzed in vitro. 3-Nitropropionic acid was administered onto the round window of guinea pigs. Cell death was identified by terminal transferase labeling the free 3′OH breaks in the DNA strands in vivo and propidium iodide nuclear permeation in vitro. As a result, 23.6 and 96.3 % cell death were induced by 10 and 100 mM 3-nitropropionic acid, respectively, in vitro. In the guinea pigs, 500 mM 3-nitropropionic acid induced vestibular dysfunction and severe to profound hearing losses. The cells that are the most sensitive to 3-nitropropionic acid treatment include the stria marginal and intermediate cells, epithelial cells of the Reissner’s membrane, and spiral ligament fibrocytes (types II and V). Moderate sensitive cells were satellite fibrocytes of the spiral limbic central zone, osteocytes of the cochlear shell, hair cells, and spiral ganglion cells. Reduction of neurofilament in the soma and periphery processes of spiral ganglion cells occurred after the exposure. These results may be relevant to the mechanisms of injury in sudden onset sensorineural hearing loss and hazardous substance exposure-induced hearing loss.