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  1. 050 医学部, 大学院医学系研究科
  2. 0507 学位論文
  3. 博士(医学)

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/10091/16029
3ad8babf-6d6a-49d3-b116-0931a54a71c8
名前 / ファイル ライセンス アクション
H23Otsu21144_nakamura.pdf H23Otsu21144_nakamura.pdf (1.1 MB)
Item type 学術雑誌論文 / Journal Article(1)
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

Nakamura-Yanagidaira, Tomoko

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Takahashi, Yasuko

× Takahashi, Yasuko

Takahashi, Yasuko

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Sano, Kenji

× Sano, Kenji

Sano, Kenji

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Murata, Toshinori

× Murata, Toshinori

Murata, Toshinori

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Hayashi, Takuma

× Hayashi, Takuma

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
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.
資源タイプ(コンテンツの種類)
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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Cite as

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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