Enhanced biosynthesis of glutathione in the spiral ganglion of the cochlea after in vivo treatment with dexamethasone in mice
Enhanced biosynthesis of glutathione in the spiral ganglion of the cochlea after in vivo treatment with dexamethasone in mice
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DOI：
10.1016/j.brainres.2006.07.113
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发表时间：
2006-10-30
期刊：
影响因子：
2.9
通讯作者：
Ogita, Kiyokazu
中科院分区：
文献类型：
--
作者：
Nagashima, Reiko;Ogita, Kiyokazu
糖皮质激素已被广泛用作突发性耳聋的治疗药物。然而，关于糖皮质激素对听力损失的保护作用的机制知之甚少。作为阐明其机制的一种方法，我们评价了地塞米松（DEX）处理对小鼠耳蜗中GSH生物合成的影响。DEX全身给药后2 ~ 24 h耳蜗总GSH水平显著升高。这种DEX诱导的GSH增加选择性地发生在螺旋神经节中，但在侧壁组织或Corti器官中不显着。此外，RT-PCR分析表明，DEX处理导致谷氨酰半胱氨酸合成酶（γ-GCS）的表达增强，这是从头GSH合成的限速酶，处理后1至24小时。除了增强GSH的生物合成外，DEX处理还有效地减少耳蜗中的脂质过氧化。总之，DEX具有通过增强耳蜗螺旋神经节中γ-GCS的表达来促进GSH生物合成的能力。(c)2006 Elsevier B. V.保留所有权利。
Glucocorticoids have been widely used as a therapeutic drug for sudden sensorineural hearing loss. However, very little is known about the mechanism(s) underlying the protective effect of glucocorticoids against hearing loss. As an approach toward elucidating the mechanism(s), we evaluated the effects of dexamethasone (DEX) treatment on the biosynthesis of GSH in the mouse cochlea in vivo. The systemic administration of DEX led to a significant increase in the total GSH level in the cochlea 2 to 24 h later. This DEX-induced increase in GSH occurred selectively in the spiral ganglion, but not significantly in the lateral wall tissues or in the organ of Corti. Furthermore, RT-PCR analysis revealed that DEX treatment resulted in enhanced expression of glutamylcysteine synthetase (gamma-GCS), which is the rate-limiting enzyme for de novo GSH synthesis, 1 to 24 h after the treatment. in addition to enhancing GSH biosynthesis, DEX treatment was effective in reducing lipid peroxidation in the cochlea. Taken together, DEX has the ability to facilitate GSH biosynthesis through enhanced expression of gamma-GCS in the cochlear spiral ganglion. (c) 2006 Elsevier B.V. All rights reserved.