Molecular mechanisms underlying cochlear degeneration in the tubby mouse and the therapeutic effect of sulforaphane

被引：27

作者：

Kong, Li ^{[1
,2
,5
]}

Chen, Guang-Di ^{[4
]}

Zhou, Xiaohong ^{[1
,2
]}

McGinnis, James F. ^{[1
,2
]}

Li, Feng ^{[1
,2
]}

Cao, Wei ^{[1
,2
,3
]}

机构：

[1] Univ Oklahoma, Hlth Sci Ctr, Dept Ophthalmol, Oklahoma City, OK 73104 USA

[2] Univ Oklahoma, Hlth Sci Ctr, Dean A McGee Eye Inst, Oklahoma City, OK 73104 USA

[3] Univ Oklahoma, Hlth Sci Ctr, Dept Physiol, Oklahoma City, OK 73104 USA

[4] SUNY Buffalo, Ctr Hearing & Deafness, Buffalo, NY 14260 USA

[5] Dalian Med Univ, Dept Histoembryol, Dalian, Liaoning, Peoples R China

来源：

NEUROCHEMISTRY INTERNATIONAL | 2009年 / 54卷 / 3-4期

关键词：

Tubby mice; Age-related hearing loss; Thioredoxin; Extracellular signal-regulated kinase; Caspase; Sulforaphane; PROSTATE-CANCER CELLS; XENOGRAFTS IN-VIVO; FREE-RADICALS; SIGNALING PATHWAYS; CRUCIFEROUS VEGETABLES; ALLYL ISOTHIOCYANATE; RETINAL DEGENERATION; PROTECTIVE AGENTS; EPITHELIAL-CELLS; PROTEIN-KINASES;

D O I：

10.1016/j.neuint.2008.08.013

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

070307 [化学生物学]; 071010 [生物化学与分子生物学];

摘要：

As with Usher syndrome observed in humans, the two main phenotypes of the tubby mouse are progressive hearing loss and retinal degeneration. Yet, the mechanism underlying the tub-related cochlear degeneration is still unclear. The reduction/oxidation (redox) imbalance in the cell is related to many kinds of diseases. This study examined expressions of thioredoxin (Trx) and Trx reductase (TrxR), an important redox system in the cell, and the related upstream and downstream proteins of the Trx/TrxR in the tubby mouse cochlea. This report also examined the therapeutic effect of sulforaphane (SF) on the cochlear degeneration, which showed a protective effect on the tub-related retinal degeneration in our previous report. The results showed that the tub-mutation resulted in a significant suppression of Trx and TrxR expressions. Expression level of Nrf2 (NFE2 related factor 2), a transcription factor that regulates expression of Trx and TrxR and others, was also suppressed in the tubby mouse cochlea. Furthermore, a lowered level of activated extracellular signal-regulated kinase (p-ERK) was observed in the tubby mouse cochlea. In contrast, caspase-3 expression and activity were enhanced in the tubby mouse, suggesting apoptotic cell death. The tub-related molecular alterations in the cochlea were prevented by chronic treatment with SF. As a result, the SF-treatment significantly delayed the tub-related cochlear degeneration. Other unknown proteins may contribute to tubby-related degeneration because Nrf2 regulates many other antioxidants besides Trx/TrxR and sulforaphane did not prevent cochlear degeneration completely although it completely prevented alterations of Nrf2 and Trx/TrxR. (C) 2008 Elsevier Ltd. All rights reserved.

引用

页码：172 / 179

页数：8

共 54 条

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