COCHLEAR PROTECTION FROM ACOUSTIC INJURY BY INHIBITORS OF p38 MITOGEN-ACTIVATED PROTEIN KINASE AND SEQUESTOSOME 1 STRESS PROTEIN
COCHLEAR PROTECTION FROM ACOUSTIC INJURY BY INHIBITORS OF p38 MITOGEN-ACTIVATED PROTEIN KINASE AND SEQUESTOSOME 1 STRESS PROTEIN
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DOI：
10.1016/j.neuroscience.2009.12.038
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发表时间：
2010-03-17
期刊：
影响因子：
3.3
通讯作者：
Hara, A.
中科院分区：
文献类型：
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作者：
Tabuchi, K.;Oikawa, K.;Hara, A.
本研究评价了p38丝裂原活化蛋白激酶(P38 MAPK)抑制剂和应激诱导的信号调节剂Sqstm1/A170/p62对小鼠耳蜗声损伤的保护作用。在小鼠暴露于声应激两周后，评估听性脑干反应(ABR)与暴露前水平的阈值偏移和毛细胞丢失。声应激后4h免疫组织化学染色观察p38MAPK在耳蜗内的激活情况。为了研究p38MAPK在组织损伤中的作用，我们采用了p38MAPK的抑制剂。给雄性野生型C57BL小鼠注射声学过度暴露前。抑制物SB202190和SB203580可剂量依赖性地降低听性听阈漂移和外毛细胞丢失，提示p38MAPK参与了耳毒性作用。我们发现，声过度暴露诱导野生型小鼠耳蜗中Sqstm1mRNA表达上调，SQSTM1缺陷小鼠表现出ABR阈值漂移和毛细胞丢失的增强，表明SQSTM1在组织保护中的作用。(C)2010 Ibro。爱思唯尔有限公司出版。保留所有权利。
This study evaluated the protective role of p38 mitogen-activated protein kinase (p38 MAPK) inhibitors and sequestosome 1 (Sqstm1/A170/p62), a stress-induced signal modulator, in acoustic injury of the cochlea in mice. Two weeks after the exposure of mice to acoustic stress, threshold shifts of the auditory brainstem response (ABR) from the pre-exposure level and hair cell loss were evaluated. The activation of p38 MAPK was observed in cochlea by immunostaining 4 h after acoustic stress. To examine the role of p38 MAPK in tissue injury, its inhibitors were i.p. injected into male wild-type C57BL mice before the acoustic overexposure. The inhibitors SB202190 and SB203580 but not the inactive analogue SB202474 dose-dependently decreased the auditory threshold shift and outer hair cell loss induced by acoustic overexposure, suggesting the involvement of p38 MAPK in ototoxicity. We found that acoustic overexposure induced the up-regulation of Sqstm1 mRNA expression in the cochlea of wild-type mice and that SQSTM1-deficient mice exhibited an enhanced ABR threshold shift and hair cell loss, suggesting a role of SQSTM1 in the protection of tissue from acoustic stress.(C) 2010 IBRO. Published by Elsevier Ltd. All rights reserved.