Regenerated hair cells exhibit a transient resistance to aminoglycoside toxicity
Regenerated hair cells exhibit a transient resistance to aminoglycoside toxicity
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DOI：
10.1016/0006-8993(95)01467-5
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发表时间：
1996-05-13
期刊：
影响因子：
2.9
通讯作者：
Salvi, RJ
中科院分区：
文献类型：
--
作者：
Hashino, E;Salvi, RJ
最近的研究表明，鸟类内耳的感觉毛细胞是通过细胞增殖来复制的，以应对原始毛细胞种群的死亡。再生的毛细胞似乎构建了功能性突触接触，从而将声信号传输到周围神经系统。这些再生毛细胞最不寻常但被忽视的特征之一是它们在高度耳毒性的环境中生存的能力。在这里，我们报告了在长期接触氨基糖苷类抗生素的情况下，卡那霉素诱导毛细胞丢失后再生的毛细胞可以比它们的前辈存活更长的雾化期。然而，存活时间的延长完全是由于再生的毛细胞处于不成熟状态。一旦再生的毛细胞达到形态成熟，它们就容易受到氨基糖苷类毒性的影响。对卡那霉素的免疫组织化学评估表明，卡那霉素可能通过受体介导的顶端表面的内吞作用进入毛细胞。相比之下，卡那霉素很少被掺入再生毛细胞的细胞质中。这些结果表明，毛细胞顶端表面受体介导的跨膜转运过程是受发育调节的，参与跨膜转运的部分组装的缺乏可能是抑制氨基糖苷摄取的原因，导致未成熟毛细胞对氨基糖苷类药物产生抗性。
Recent studies have demonstrated that sensory hair cells in the avian inner ear are reproduced by cell proliferation in response to the death of the original hair cell population. The regenerated hair cells appear to construct functional synaptic contacts, thereby transmitting acoustic signals to the peripheral nervous system. One of the most extraordinary, but overlooked characteristics of these regenerated hair cells, is their ability to survive in a highly ototoxic environment. Here, we report that hair cells regenerated after kanamycin induced hair cell loss can survive for a substantially longer rime period than their predecessors during prolonged exposure to aminoglycoside antibiotics. The prolonged survival, however, belongs solely to the immature status of regenerated hair cells. Once the regenerated hair cells reach morphological maturation, they become vulnerable to aminoglycoside toxicity. Immunohistochemical evaluation of kanamycin suggested that kanamycin may be taken up into hair cells via a receptor-mediated endocytosis at their apical surfaces. By contrast, kanamycin was rarely incorporated into the cytoplasm of the regenerated hair cells. These results suggest that the process of a receptor-mediated transmembrane transport at the apical surface of hair cells is developmentally regulated, and that the lack of some of the assembly involved in the transmembrane transport could be responsible for the inhibition of aminoglycoside uptake, leading immature hair cells to be aminoglycoside resistant.