演題詳細

一般口演 / Oral Session

一般口演 91 (Oral Session 91) :AML:細胞の特性 2

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日程
2013年10月13日(日)
時間
16:00 - 17:00
会場
第3会場 / Room No.3 (さっぽろ芸文館 3F 蓬莱)
座長・司会
矢野 道広 (Michihiro Yano):1
1:秋田大学医学部 小児科
 
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ROS has a key role in proliferation of leukemia cells under hypoxia

演題番号 : OS-3-101

後藤 峰明 (Mineaki Goto):1、三輪 啓志 (Hiroshi Miwa):1、爾見 雅人 (Masato Shikami):2、恒川 敬和 (Norikazu Tsunekawa):1、菅沼 和人 (Kazuto Suganuma):1、内野 かおり (Kaori Uchino):1、堀尾 知弘 (Tomohiro Horio):1、水谷 元紀 (Motonori Mizutani):1、高橋 美裕希 (Miyuki Takahashi):1、水野 昌平 (Shohei Mizuno):1、後藤 麻友子 (Mayuko Goto):1、山本 英督 (Hidesuke Yamamoto):1、若林 基弘 (Motohiro Wakabayashi):1、渡會 雅也 (Masaya Watarai):1、花村 一朗 (Ichiro Hanamura):1、今村 明 (Akira Imamura):1、三原 英嗣 (Hidetsugu Mihara):1、仁田 正和 (Masakazu Nitta):1

1:Dept. Hematol., Aichi Medical Univ., Japan、2:Dept. Hematol., General Daiyukai Hospital, Japan

 

We demonstrated the proliferation of leukemia cells under hypoxia (JSH 2012 1-38). Here, we examined the influence of reactive oxygen species (ROS) on leukemia cell proliferation and survival under hypoxia. NB4 under hypoxia showed a significant poorer proliferation than under normoxia as a consequence of increased apoptosis, but THP1 under hypoxia significantly more proliferated than under normoxia. ROS level was much higher in NB4 under 48 hours hypoxia than normoxia. Incubation with N-acetyl-L-cysteine (NAC) as ROS scavenger decreased ROS and subsequently apoptosis in NB4 under hypoxia. GSH / GSSG ratio also suggested NB4 under hypoxia had much oxidative stress. However, NB4 under much longer hypoxia (2 weeks) had lower oxidative stress than 48 hours hypoxia. This might be explained by upregulation of glutamate-cysteine ligase (GSH formation) under hypoxia. On the other hand, THP1 did not show increase of ROS and oxidative stress under hypoxia. It was demonstrated that THP1 under hypoxia showed upregulation of pyruvate dehydrogenase kinase 1 which inactivates mitochondrial pyruvate dehydrogenase and suppresses the entry into TCA cycle. Alternatively, THP1 under hypoxia made downregulation of cytochrome c oxidase subunit 4 (COX4) isoform 1 and upregulation of COX4 isoform 2. ROS had key role in proliferation of leukemia cells under hypoxia and leukemia cells also had some ways to overcome these stress such as COX4 switching (efficient respiration at different O2 concentration).

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