title: Differential cellular localization of antioxidant enzymes in the trigeminal ganglion.
abstract: Because of its high oxygen demands, neural tissue is predisposed to oxidative stress. Here, our aim was to clarify the cellular localization of antioxidant enzymes in the trigeminal ganglion. We found that the transcriptional factor Sox10 is localized exclusively in satellite glial cells (SGCs) in the adult trigeminal ganglion. The use of transgenic mice that express the fluorescent protein Venus under the Sox10 promoter enabled us to distinguish between neurons and SGCs. Although both superoxide dismutases 1 and 2 were present in the neurons, only superoxide dismutase 1 was identified in SGCs. The enzymes relevant to hydrogen peroxide degradation displayed differential cellular localization, such that neurons were endowed with glutathione peroxidase 1 and thioredoxin 2, and catalase and thioredoxin 2 were present in SGCs. Our immunohistochemical finding showed that only SGCs were labeled by the oxidative damage marker 8-hydroxy-2'-deoxyguanosine, which indicates that the antioxidant systems of SGCs were less potent. The transient receptor potential vanilloid subfamily member 1 (TRPV1), the capsaicin receptor, is implicated in inflammatory hyperalgesia, and we demonstrated that topical capsaicin application causes short-lasting mechanical hyperalgesia in the face. Our cell-based assay revealed that TRPV1 agonist stimulation in the presence of TRPV1 overexpression caused reactive oxygen species-mediated caspase-3 activation. Moreover, capsaicin induced the cellular demise of primary TRPV1-positive trigeminal ganglion neurons in a dose-dependent manner, and this effect was inhibited by a free radical scavenger and a pancaspase inhibitor. This study delineates the localization of antioxidative stress-related enzymes in the trigeminal ganglion and reveals the importance of the pivotal role of reactive oxygen species in the TRPV1-mediated caspase-dependent cell death of trigeminal ganglion neurons. Therapeutic measures for antioxidative stress should be taken to prevent damage to trigeminal primary sensory neurons in inflammatory pain disorders.
authors.affiliation: Department of Neurology, School of Medicine, Keio University, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan; Department of Dentistry and Oral Surgery, School of Medicine, Keio University, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan; Japan Society for the Promotion of Science, 8 Ichiban-cho, Chiyoda-ku, Tokyo 102-8472, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Sato
authors.affiliation: Department of Neurology, School of Medicine, Keio University, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan. Electronic address: mshibata@a7.keio.jp.
authors.forename: M
authors.initials: M
authors.lastname: Shibata
authors.affiliation: Department of Neurology, School of Medicine, Keio University, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Shimizu
authors.affiliation: Department of Physiology, School of Medicine, Keio University, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Shibata
authors.affiliation: Department of Neurology, School of Medicine, Keio University, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Toriumi
authors.affiliation: Department of Neurology, School of Medicine, Keio University, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Ebine
authors.affiliation: Department of Neurology, School of Medicine, Keio University, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Kuroi
authors.affiliation: Department of Neurology, School of Medicine, Keio University, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Iwashita
authors.affiliation: Department of Neurology, School of Medicine, Keio University, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Funakubo
authors.affiliation: Department of Neurology, School of Medicine, Keio University, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Kayama
authors.affiliation: Department of Biochemistry and Biophysics, Graduate School of Health and Sciences, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8510, Japan.
authors.forename: C
authors.initials: C
authors.lastname: Akazawa
authors.affiliation: Department of Dentistry and Oral Surgery, School of Medicine, Keio University, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Wajima
authors.affiliation: Department of Dentistry and Oral Surgery, School of Medicine, Keio University, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Nakagawa
authors.affiliation: Department of Physiology, School of Medicine, Keio University, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Okano
authors.affiliation: Department of Neurology, School of Medicine, Keio University, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan.
authors.forename: N
authors.initials: N
authors.lastname: Suzuki
mesh_terms: D000080242:8-Hydroxy-2'-Deoxyguanosine; D000818:Animals; D002211:Capsaicin / Q000009:adverse effects; D002374:Catalase / Q000378:metabolism; D003849:Deoxyguanosine / Q000008:administration & dosage / Q000031:analogs & derivatives; D005456:Fluorescent Dyes / Q000737:chemistry; D005979:Glutathione Peroxidase / Q000378:metabolism; D006930:Hyperalgesia / Q000139:chemically induced; D007150:Immunohistochemistry; D051379:Mice; D008822:Mice, Transgenic; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D018384:Oxidative Stress / Q000187:drug effects*; D011401:Promoter Regions, Genetic / Q000187:drug effects; D055757:SOXE Transcription Factors / Q000235:genetics; D027161:Satellite Cells, Perineuronal / Q000187:drug effects / Q000378:metabolism*; D050916:TRPV Cation Channels / Q000378:metabolism; D013879:Thioredoxins / Q000378:metabolism; D012668:Trigeminal Ganglion / Q000166:cytology*; D000094765:Glutathione Peroxidase GPX1
chemical_list: D005456:Fluorescent Dyes; D055757:SOXE Transcription Factors; C527924:Sox10 protein, mouse; D050916:TRPV Cation Channels; C493921:TRPV1 protein, mouse; D013879:Thioredoxins; D000080242:8-Hydroxy-2'-Deoxyguanosine; C492172:Gpx2 protein, mouse; D002374:Catalase; D005979:Glutathione Peroxidase; D003849:Deoxyguanosine; D002211:Capsaicin; D000094765:Glutathione Peroxidase GPX1; C000722068:Gpx1 protein, mouse
keywords: catalase; glutathione peroxidase; inflammatory pain; transient receptor potential vanilloid subfamily member 1, caspase; trigeminal ganglion