Endocytosis of aminoglycoside antibiotics in sensory hair cells
Endocytosis of aminoglycoside antibiotics in sensory hair cells
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DOI：
10.1016/0006-8993(95)01198-6
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发表时间：
1995-12-15
期刊：
影响因子：
2.9
通讯作者：
Shero, M
中科院分区：
文献类型：
--
作者：
Hashino, E;Shero, M
用免疫金电子显微镜观察感觉毛细胞对氨基糖苷类抗生素卡那霉素(KM)的摄取途径。全身注射KM后12h，毛细胞质膜上及毛细胞根尖下光滑的大小泡内均可见明显的金颗粒聚集。免疫金蛋白仅定位于注射后27h的囊泡中。阳离子铁蛋白是一种膜结合型不溶性标记物，在体外同时应用后，与Km共定位于囊泡结构中。这些结果强烈地表明KM是通过受体介导的顶端表面的内吞作用进入感觉毛细胞的。此外，KM摄取和毛细胞死亡之间的深刻时间间隔表明靶向机制参与了药物的细胞毒信号通路。
Immuno-gold electron microscopy was used to assess the uptake pathways of aminoglycoside antibiotic kanamycin (KM) in sensory hair cells. Accumulation of gold particles was evident on the plasma membrane as well as in large smooth vesicles beneath the apical surfaces of hair cells 12 h after a systemic administration of KM. Immune-gold was exclusively localized in the vesicles 27 h post-injection. Cationic ferritin, a membrane-bound insoluble marker, was colocalized with KM in the vesicle structures after their simultaneous in vitro application. These results strongly suggest that KM is taken up into sensory hair cells via receptor-mediated endocytosis at their apical surfaces. In addition, the profound time lag between KM uptake and hair cell death suggests involvement of targeting mechanisms in cytotoxic signalling pathways of the drugs.