Critical signaling events during the aminoglycoside-induced death of sensory hair cells in vitro
Critical signaling events during the aminoglycoside-induced death of sensory hair cells in vitro
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DOI：
10.1002/neu.20054
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发表时间：
2004-11-01
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影响因子：
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通讯作者：
Warchol, ME
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作者：
Matsui, JI;Gale, JE;Warchol, ME
氨基糖苷类抗生素暴露后感觉毛细胞发生凋亡。在神经元中，细胞凋亡与细胞内Ca 2+的瞬时增加、转录因子c-Jun的磷酸化以及细胞色素c从线粒体释放到胞质溶胶中相关，细胞色素c沿着其他辅因子导致半胱天冬酶的激活。为了研究这些事件在内耳感觉受体的存活和死亡中的可能作用，我们研究了新霉素处理对培养的前庭毛细胞中细胞质钙、c-Jun-N-末端激酶（JNKs）激活、细胞色素c释放和caspase-3激活 * 的影响。在新霉素处理后3-12 h观察到磷酸-c-jun标记的毛细胞（JNK活化的下游指标）数量增加，而在新霉素处理开始后12-18 h观察到细胞质细胞色素c的细胞数量增加。随后是含有活化的半胱天冬酶-3并显示核固缩的细胞数量增加。用一般的caspase抑制剂BAF处理不影响细胞色素c的释放和p-c-Jun-labeled细胞的数量，但减少了具有活化的caspase-3和固缩核的细胞的数量。
Sensory hair cells undergo apoptosis following exposure to aminoglycoside antibiotics. In neurons, apoptosis is associated with a transient increase in intracellular Ca2+, phosphorylation of the transcription factor c-Jun, and the release of cytochrome c from mitochondria into the cytosol, which along with other cofactors results in the activation of caspases. To examine the possible role of these events in the survival and death of the sensory receptors of the inner ear, we examined the effects of neomycin treatment on cytoplasmic calcium, activation of c-Jun-N-Terminal kinases (JNKs), cytochrome c release, and caspase-3 activation * in cultured vestibular hair cells. Increased numbers of phospho-c-jun-labeled hair cells (a downstream indicator of JNK activation) were observed at 3-12 h after neomycin treatment, whereas increased numbers of cells with cytoplasmic cytochrome c were observed at 12-18 h following the onset of neomycin treatment. This was followed by an increase in the number of cells that contained activated caspase-3 and displayed pyknotic nuclei. Treatment with the general caspase inhibitor BAF did not affect the release of cytochrome c and the number of p-c-Jun-labeled cells, but reduced the number of cells with activated caspase-3 and pyknotic nuclei.