| NOX3 NADPH oxidase couples transient receptor potential vanilloid 1 to signal transducer and activator of transcription 1-mediated inflammation and hearing loss. | |
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MedLine Citation:
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PMID: 20712533 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Transient receptor potential vanilloid 1 (TRPV1) is implicated in cisplatin ototoxicity. Activation of this channel by cisplatin increases reactive oxygen species generation, which contribute to loss of outer hair cells in the cochlea. Knockdown of TRPV1 by short interfering RNA protected against cisplatin ototoxicity. In this study, we examined the mechanism underlying TRPV1-mediated ototoxicity using cultured organ of Corti transformed cells (UB/OC-1) and rats. Trans-tympanic injections of capsaicin produced transient hearing loss within 24 h, which recovered by 72 h. In UB/OC-1 cells, capsaicin increased NOX3 NADPH oxidase activity and activation of signal transducer and activator of transcription 1 (STAT1). Intratympanic administration of capsaicin transiently increased STAT1 activity and expression of downstream proinflammatory molecules. Capsaicin produced a transient increase in CD14-positive inflammatory cells into the cochlea, which mimicked the temporal course of STAT1 activation but did not alter the expression of apoptotic genes or damage to outer hair cells. In addition, trans-tympanic administration of STAT1 short interfering RNA protected against capsaicin-induced hearing loss. These data suggest that activation of TRPV1 mediates temporary hearing loss by initiating an inflammatory process in the cochlea via activation of NOX3 and STAT1. Thus, these proteins represent reasonable targets for ameliorating hearing loss. |
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Authors:
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Debashree Mukherjea; Sarvesh Jajoo; Kelly Sheehan; Tejbeer Kaur; Sandeep Sheth; Jennifer Bunch; Christopher Perro; Leonard P Rybak; Vickram Ramkumar |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2010-12-07 |
Journal Detail:
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Title: Antioxidants & redox signaling Volume: 14 ISSN: 1557-7716 ISO Abbreviation: Antioxid. Redox Signal. Publication Date: 2011 Mar |
Date Detail:
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Created Date: 2011-02-21 Completed Date: 2011-07-01 Revised Date: 2012-03-15 |
Medline Journal Info:
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Nlm Unique ID: 100888899 Medline TA: Antioxid Redox Signal Country: United States |
Other Details:
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Languages: eng Pagination: 999-1010 Citation Subset: IM |
Affiliation:
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Department of Pharmacology, SIU School of Medicine, Springfield, Illinois 62794-9629, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Capsaicin / administration & dosage, pharmacology* Cells, Cultured Cochlea / drug effects, metabolism Evoked Potentials Hearing Loss / chemically induced, metabolism* Immunohistochemistry Inflammation / genetics, metabolism* Male Mice Microscopy, Electron, Scanning NADPH Oxidase / genetics, metabolism* RNA, Small Interfering / drug effects, genetics Rats Rats, Wistar Reactive Oxygen Species / metabolism Reverse Transcriptase Polymerase Chain Reaction STAT1 Transcription Factor / genetics, metabolism* TRPV Cation Channels / genetics, metabolism* |
| Grant Support | |
ID/Acronym/Agency:
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CA135494/CA/NCI NIH HHS; DC02396/DC/NIDCD NIH HHS; F32 DC009950/DC/NIDCD NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/RNA, Small Interfering; 0/Reactive Oxygen Species; 0/STAT1 Transcription Factor; 0/TRPV Cation Channels; 0/vanilloid receptor subtype 1; 404-86-4/Capsaicin; EC 1.6.3.1/NADPH Oxidase |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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