The role of peroxiredoxin I in cisplatin-induced ototoxicity.
OBJECTIVE
Peroxiredoxin (Prx) is a new family of antioxidative proteins. Prx I is ubiquitously expressed in various tissues and is important in the defense of tissues from increases in reactive oxygen species (ROS). The present study was designed to examine the expression of Prx subtypes in the mouse cochlea and to show the possible involvement of Prx I in protecting the cochlea against cisplatin ototoxicity.


METHODS
Postnatal-day-3-to-5 wildtype mice and Prx I-deficient mice were used. Prx expression in the cochlea was assessed by real-time PCR assay. Prx I protein expression was examined by immunofluorescence staining. Cochlear explants were exposed to 2, 5, and 10-μM cisplatin for 48h, and the cochlear hair cell losses of the wildtype and Prx I-deficient mice were compared. In addition, the histologic features of the cochlear lateral wall were examined after cisplatin incubation.


RESULTS
mRNAs of all Prx subtypes were expressed in the mouse cochlea. Prx I was one of the abundant subtypes and was upregulated after 48-h exposure to 5-μM cisplatin. Immunofluorescence staining showed the ubiquitous expression of Prx I in the cochlea. No difference in cochlear hair cell loss induced by cisplatin was found between the wildtype mice and the Prx I-deficient mice. However, spiral ligament fibrocytes of Prx I-deficient mice were significantly sensitive to cisplatin at 20-μM or lower.


CONCLUSIONS
Prx I is important for protection of at least the spiral ligament fibrocytes of the cochlear lateral wall in cisplatin ototoxicity.
Doctoral Program in Biomedical Sciences, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Japan.
Quang
Q
Le
Department of Otolaryngology, Faculty of Medicine, University of Tsukuba, Japan. Electronic address: ktabuchi@md.tsukuba.ac.jp.
Keiji
K
Tabuchi
Institute of Community Medicine, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Japan.
Eiji
E
Warabi
Department of Otolaryngology, Faculty of Medicine, University of Tsukuba, Japan.
Akira
A
Hara
D000818:Animals; D000970:Antineoplastic Agents / Q000633:toxicity*; D002945:Cisplatin / Q000633:toxicity*; D003051:Cochlea / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D005455:Fluorescent Antibody Technique; D006198:Hair Cells, Auditory / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D054464:Peroxiredoxins / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000187:drug effects* / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction
D000970:Antineoplastic Agents; D012333:RNA, Messenger; D054464:Peroxiredoxins; D002945:Cisplatin
Cisplatin; Cochlear hair cells; Ototoxicity; Peroxiredoxin; Spiral ligaments fibrocytes