QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

HOME  |   SEARCH  |   ARCHIVE  |   SUBSCRIBE  |   CONTACT  |   HELP

The Journal of Neuroscience, March 25, 2009, 29(12):3843-3851; doi:10.1523/JNEUROSCI.5842-08.2009

This Article Full Text Full Text (PDF) Submit an eLetter Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Related articles in J. Neurosci. Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Schmitt, N. C. Articles by Nathanson, N. M. Search for Related Content PubMed PubMed Citation Articles by Schmitt, N. C. Articles by Nathanson, N. M.

 Previous Article  |  Next Article 

Neurobiology of Disease
Cisplatin-Induced Hair Cell Death Requires STAT1 and Is Attenuated by Epigallocatechin Gallate

Nicole C. Schmitt,^1,2 Edwin W Rubel,^1,2 and Neil M. Nathanson^1,3

¹Virginia Merrill Bloedel Hearing Research Center, ²Department of Otolaryngology, Head and Neck Surgery, and ³Department of Pharmacology, University of Washington, Seattle, Washington 98195

Correspondence should be addressed to Edwin W Rubel, Virginia Merrill Bloedel Hearing Research Center, Mail Stop 357923, University of Washington, Seattle, WA 98195. Email: rubel{at}u.washington.edu

Cisplatin is a chemotherapy drug that frequently causes auditory impairment due to the death of mechanosensory hair cells. Cisplatin ototoxicity may result from oxidative stress, DNA damage, and inflammatory cytokines. The transcription factor STAT1, an important mediator of cell death, can regulate all of these processes in other cell types. We used cultured utricles from mature Swiss Webster mice to investigate the role of STAT1 in cisplatin-induced hair cell death. We show that STAT1 phosphorylation is an early event in both hair cells and support cells after exposure of utricles to cisplatin. STAT1 phosphorylation peaked after 4 h of cisplatin exposure and returned to control levels by 8 h of exposure. The STAT1 inhibitor epigallocatechin gallate (EGCG) attenuated STAT1 phosphorylation in cisplatin-treated utricles and resulted in concentration-dependent increases in hair cell survival at 24 h postexposure. Furthermore, we show that utricular hair cells from STAT1-deficient mice are resistant to cisplatin toxicity. EGCG failed to provide additional protection from cisplatin in STAT1-deficient mice, further supporting the hypothesis that the protective effects of EGCG are due to its inhibition of STAT1. Treatment with IFN-, which also causes STAT1 activation, also induced hair cell death in wild-type but not STAT1-deficient mice. These results show that STAT1 is required for maximal cisplatin-induced hair cell death in the mouse utricle and suggest that treatment with EGCG may be a useful strategy for prevention of cisplatin ototoxicity.

---

Received Dec. 8, 2008; accepted Jan. 7, 2009.

Correspondence should be addressed to Edwin W Rubel, Virginia Merrill Bloedel Hearing Research Center, Mail Stop 357923, University of Washington, Seattle, WA 98195. Email: rubel{at}u.washington.edu

Related articles in J. Neurosci.:

This Week in The Journal

J. Neurosci. 2009 29: i. [Full Text]  

Home  |   Search  |   Archive  |   Subscribe  |   Contact  |   Help