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Development of spontaneous neuropathy in NF-kappa Bp50-deficient mice by calcineurin-signal involving impaired NF-kappa B activation
http://hdl.handle.net/10091/16029
http://hdl.handle.net/10091/160293ad8babf-6d6a-49d3-b116-0931a54a71c8
| 名前 / ファイル | ライセンス | アクション |
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H23Otsu21144_nakamura.pdf (1.1 MB)
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| Item type | 学術雑誌論文 / Journal Article(1) | |||||||||||||||
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| 公開日 | 2012-10-03 | |||||||||||||||
| タイトル | ||||||||||||||||
| タイトル | Development of spontaneous neuropathy in NF-kappa Bp50-deficient mice by calcineurin-signal involving impaired NF-kappa B activation | |||||||||||||||
| 言語 | ||||||||||||||||
| 言語 | eng | |||||||||||||||
| 資源タイプ | ||||||||||||||||
| 資源 | http://purl.org/coar/resource_type/c_6501 | |||||||||||||||
| タイプ | journal article | |||||||||||||||
| 著者 |
Nakamura-Yanagidaira, Tomoko
× Nakamura-Yanagidaira, Tomoko
× Takahashi, Yasuko
× Sano, Kenji
× Murata, Toshinori
× Hayashi, Takuma
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| 信州大学研究者総覧へのリンク | ||||||||||||||||
| 氏名 | Murata, Toshinori | |||||||||||||||
| URL | http://soar-rd.shinshu-u.ac.jp/profile/ja.jpApONfU.html | |||||||||||||||
| 出版者 | ||||||||||||||||
| 出版者 | MOLECULAR VISION | |||||||||||||||
| 引用 | ||||||||||||||||
| 内容記述 | MOLECULAR VISION. 17:2157-2170 (2011) | |||||||||||||||
| 書誌情報 |
MOLECULAR VISION 巻 17, p. 2157-2170, 発行日 2011-08-11 |
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| 内容記述 | ||||||||||||||||
| 内容記述タイプ | Other | |||||||||||||||
| 内容記述 | 信州大学博士（医学）・学位論文・平成24年3月28日授与（乙第21144号）・中村朋子 | |||||||||||||||
| 抄録 | ||||||||||||||||
| 内容記述 | Purpose: The transcriptional regulator, nuclear factor-kappa B (NF-kappa B)/Rel family are involved in neuronal cell death and survival. Previously, we reported that NF-kappa Bp50-deficient (p50-deficient) mice exhibit many features resembling human normal tension glaucoma (NTG). The developmental mechanism of human NTG is not clearly understood, and a radical curative treatment has yet to be established. Our aim is to elucidate the signal cascade which mediates the spontaneous optic neuropathy in p50-deficient mice as a model of NTG. Methods: To demonstrate the expression and activation of pro-apoptotic factors, which mediate the death of retinal ganglion cells (RGCs) in p50-deficient mice, western blot (WB) and luciferase reporter assays with retinas from p50-deficient and wild type mice, and cultured RGC-5 cells were performed. Furthermore, we tested the neuroprotective effects of chemical reagents (memantine, lomerizine, and tacrolimus) against N-methyl-D-aspartate (NMDA)-susceptible RGC damage according to in vitro experiments with RGC-5 cells. To elucidate the NF-kappa B-mediated death signaling, the effects of chemical reagents on spontaneous optic neuropathy were examined by histopathological studies. Results: WB experiments and luciferase reporter assays showed that NF-kappa B-inducible BCL2-associated X protein (Bax) and a pro-apoptotic factor, activated caspase 3 were expressed in the retina of p50-deficient mice as well as NMDA-treated RGC-5 cells. Further, the constitutively active cleaved forms of calcineurin (CaN), which have been reported to lead to apoptosis, were detected in the retina of p50-deficient mice as well as NMDA-treated RGC-5 cells. Pre-treatment with tacrolimus markedly protected RGC-5 cells from NMDA-induced neurotoxicity, and then both spontaneous RGC death and degenerative changes to the optic nerve in p50-deficient mice were significantly reduced by the chronic administration of tacrolimus. The experiments with cultured RGC-5 cells supported the results of histological examinations with p50-deficient mice, suggesting that CaN activation leads to NF-kappa B-induced Bax activation and caspase 3 activation, and mediates spontaneous optic neuropathy in p50-deficient mice. Conclusions: Research findings show that the chronic administration of tacrolimus significantly reduces spontaneous optic neuropathy in p50-deficient mice. We demonstrated a potential CaN signal cascade, which spontaneously induces age-dependent RGC death and degenerative optic nerve changes in p50-deficient mice. | |||||||||||||||
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| ISSN | ||||||||||||||||
| 収録物識別子タイプ | ISSN | |||||||||||||||
| 収録物識別子 | 1090-0535 | |||||||||||||||
| 書誌レコードID | ||||||||||||||||
| 収録物識別子タイプ | NCID | |||||||||||||||
| 収録物識別子 | AA12037116 | |||||||||||||||
| 異版である | ||||||||||||||||
| 関連タイプ | isVersionOf | |||||||||||||||
| 識別子タイプ | URI | |||||||||||||||
| 関連識別子 | http://www.molvis.org/molvis/v17/a234 | |||||||||||||||
| 出版タイプ | ||||||||||||||||
| 出版タイプ | VoR | |||||||||||||||
| 出版タイプResource | http://purl.org/coar/version/c_970fb48d4fbd8a85 | |||||||||||||||
| WoS | ||||||||||||||||
| URL | http://gateway.isiknowledge.com/gateway/Gateway.cgi?&GWVersion=2&SrcAuth=ShinshuUniv&SrcApp=ShinshuUniv&DestLinkType=FullRecord&DestApp=WOS&KeyUT=000293884200003 | |||||||||||||||
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Nakamura-Yanagidaira, Tomoko, Takahashi, Yasuko, Sano, Kenji, Murata, Toshinori, Hayashi, Takuma, 2011, Development of spontaneous neuropathy in NF-kappa Bp50-deficient mice by calcineurin-signal involving impaired NF-kappa B activation: MOLECULAR VISION, 2157–2170 p.
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