Overexpression of copper/zinc-superoxide dismutase protects from kanamycin-induced hearing loss
Overexpression of copper/zinc-superoxide dismutase protects from kanamycin-induced hearing loss
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DOI：
10.1159/000046818
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发表时间：
2001-05-01
影响因子：
1.6
通讯作者：
Schacht, J
中科院分区：
文献类型：
--
作者：
Sha, SH;Zajic, G;Schacht, J
通过观察氨基糖苷铁络合物在体外催化超氧阴离子自由基的形成，以及抗氧化剂在体内减轻耳毒性，推测了活性氧物种参与了氨基糖苷类耳毒性。因此，我们推测铜/锌超氧化物歧化酶(h-SOD1)的过表达应该可以保护转基因小鼠免受耳毒性。免疫细胞化学证实h-SOD1在转基因C57BL/6-TGN[SOD1]3Cje小鼠内耳组织中有表达。转基因和非转基因小鼠从出生后第10天开始注射卡那霉素(400 mg/kg体重/天)，连续10天。于出生后1个月进行听性脑干诱发反应听阈测试。在非转基因动物中，卡那霉素处理组的阈值比注射生理盐水的对照组高出45-50分贝。在转基因组，卡那霉素组的阈值仅比各自的对照组提高了15dB。在12千赫和24千赫时的影响是相似的。超氧化物歧化酶过度表达的保护作用支持氧化应激在氨基糖苷类耳毒性中起重要作用的假说。结果还表明，转基因动物是研究其潜在机制和可能的预防策略的合适模型。版权所有(C)2001 S.Karger AG，巴塞尔。
The participation of reactive oxygen species in aminoglycoside-induced ototoxicity has been deduced from observations that aminoglycoside-iron complexes catalyze the formation of superoxide radicals in vitro and that antioxidants attenuate ototoxicity in vivo. We therefore hypothesized that overexpression of Cu/Zn-superoxide dismutase (h-SOD1) should protect transgenic mice from ototoxicity. Immunocytochemistry confirmed expression of h-SOD1 in inner ear tissues of transgenic C57BL/6-TgN[SOD1]3Cje mice. Transgenic and nontransgenic littermates received kanamycin (400 mg/kg body weight/day) for 10 days beginning on day 10 after birth. Auditory thresholds were tested by evoked auditory brain stem responses at 1 month after birth. In nontransgenic animals, the threshold in the kanamycin-treated group was 45-50 dB higher than in saline-injected controls. In the transgenic group, kanamycin increased the threshold by only 15 dB over the respective controls. The effects were similar at 12 and 24 kHz. The protection by overexpression of superoxide dismutase supports the hypothesis that oxidant stress plays a significant role in aminoglycoside-induced ototoxicity. The results also suggest transgenic animals as suitable models to investigate the underlying mechanisms and possible strategies for prevention. Copyright (C) 2001 S. Karger AG, Basel.