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ミキ ヒサノリ
MIKI HISANORI 三城 弥範 所属 関西医科大学 下部消化管外科学講座 職種 診療講師 |
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| 言語種別 | 英語 |
| 発表タイトル | Calpain inhibition restores basal autophagy and suppresses apoptosis
on MNU-induced photoreceptor cell injury in mice |
| 会議名 | Association for Reseach in Vision and Ophthalmology |
| 学会区分 | 国際学会及び海外の学会 |
| 発表形式 | 口頭 |
| 講演区分 | 一般 |
| 発表者・共同発表者 | ◎Kuro M, Yoshizawa K, Uehara N, Miki H, Takahashi K, Tsubura A |
| 発表年月日 | 2011/05 |
| 開催地 （都市, 国名） |
Fort Lauderdale, Florida |
| 学会抄録 | Program 4352 2011 |
| 概要 | [Purpose] A single systemic administration of N-methyl-N-nitrosourea (MNU) causes retinal degeneration involving photoreceptor cell death within 7 days. MNU-induced photoreceptor cell death is due to apoptosis and is a reliable animal model for human retinitis pigmentosa. The purpose of this study was to elucidate the involvement of calpain-mediated autophagy as well as apoptosis on the cell death cascade caused by MNU, and to evaluate the efficacy of calpain inhibitor SNJ-1945.
[Methods] Seven-week-old BALB/c mice were left untreated or received an intraperitoneal (ip) injection of MNU, and MNU-exposed mice were treated with ip injection of SNJ-1945 or with vehicle (distilled water containing 0.5% carboxymethyl cellulose) 3 hr prior to MNU and thereafter once daily until sacrifice. Eyes were examined histologically, histochemically, and morphometrically analyzed photoreceptor cell ratio and retinal damage ratio. Extracted retinal proteins were examined for the expression of caspase-3, microtubule-associated protein light chain 3 (LC3), autophagy-related protein 5 (Atg5), and -spectrin by Western blot analysis. [Results] During 3days after MNU exposure, compared with the MNU-untreated control retina, caspase-3 expression increased , LC3 expression decreased, and Atg5 expression decreased at 24hr after MNU exprosure indicating increased apoptosis and decreased autophagy levels. MNU-induced photoreceptor cell death was caused by increased calpain activation as measured by -spectrin proteolysis products, while SNJ-1945 ameliorated photoreceptor cell death through blocking calpain activation and by restoring basal autophagy. [Conclusions]Calpain activation is involved in MNU-induced photoreceptor cell death and calpain inhibition effectively restored photoreceptor cell autophagy, suppressed apoptosis, and rescued photoreceptor cell death in mice. |