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Lithium chloride reduces radiation-induced intestinal injury through inhibiting apoptosis in intestinal epithelial cells
https://repo.qst.go.jp/records/69327
https://repo.qst.go.jp/records/69327e4383f8b-6d6b-4d25-86d9-7b7eaeba9402
| Item type | 会議発表用資料 / Presentation(1) | |||||
|---|---|---|---|---|---|---|
| 公開日 | 2008-04-21 | |||||
| タイトル | ||||||
| タイトル | Lithium chloride reduces radiation-induced intestinal injury through inhibiting apoptosis in intestinal epithelial cells | |||||
| 言語 | ||||||
| 言語 | eng | |||||
| 資源タイプ | ||||||
| 資源タイプ識別子 | http://purl.org/coar/resource_type/c_c94f | |||||
| 資源タイプ | conference object | |||||
| アクセス権 | ||||||
| アクセス権 | metadata only access | |||||
| アクセス権URI | http://purl.org/coar/access_right/c_14cb | |||||
| 著者 |
Sakaguchi, Nagako
× Sakaguchi, Nagako× 坂口 奈賀子 |
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| 抄録 | ||||||
| 内容記述タイプ | Abstract | |||||
| 内容記述 | High dose radiation induces apoptosis of intestinal epithelial cells and subsequent depletion of the stem cells, resulting in lethal gastro-intestinal injury. However, effective treatment of this injury has not been established yet. Lithium chloride (LiCl) is well known to activate Wnt signal by inhibiting the activity of glycogen synthase kinase 3 (GSK3). The Wnt signal pathway has been shown to be associated with the maintenance of the stem cells of the intestinal crypt. Moreover, LiCl has been reported to inhibit neuronal apoptosis. The present study was designed to investigate effect of LiCl on intestinal injury induced by high dose radiation. Rat small intestinal epithelial cell line, IEC-6 cells and intestinal epithelial cells in primary culture obtained from 17.5-day fetal rat duodenum were used for in vitro assays. The cells were treated with LiCl 1 hr either before or after gamma-radiation of 20 Gy, and then cultured at 37˚C until 24 hr. The apoptosis was evaluated by the Hoechst33258 staining of cells. Pretreatment with 10 mM of LiCl markedly inhibited radiation-induced apoptosis in IEC-6 cells. Addition of LiCl to these cells after radiation also blocked the apoptosis. The anti-apoptotic effect of LiCl was also found in intestinal epithelial cells in primary culture. Inhibition of either phosphoinositide 3-kinase (PI3K)/Akt or mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) kinase (MEK)/ERK pathway abrogated the anti-apoptotic effect of LiCl. In contrast, treatment with a p38 MAPK inhibitor did not affect the apoptosis. Western blot analyses showed that LiCl inhibited activation of caspase-3 and an increase of Bax level in radiated cells. Moreover, LiCl increased levels of Bcl-2 and Bcl-xL even in radiated cells. We also administered LiCl to male Balb/c mice intraperitoneally an hour prior to total-body irradiation (TBI) with 8 Gy. The numbers of crypts per circumference in jejunum were counted 3.5-day after TBI. The numbers of surviving crypts were greater in mice treated with 200 mg/kg body weight of LiCl than control mice with PBS. Thus, our results suggest that LiCl protects and rescues intestinal epithelial cells from radiation-induced apoptosis through activation of pathways involving PI3K/Akt and MEK/ERK. We also showed that LiCl reduced radiation-induced intestinal injury in vivo. | |||||
| 会議概要（会議名, 開催地, 会期, 主催者等） | ||||||
| 内容記述タイプ | Other | |||||
| 内容記述 | AACR Annual Meeting 2008 | |||||
| 発表年月日 | ||||||
| 日付 | 2008-04-18 | |||||
| 日付タイプ | Issued | |||||
