Mitochondria-targeted antioxidant enzyme activity regulates radioresistance in human pancreatic cancer cells.
Mitochondria-targeted antioxidant enzyme activity regulates radioresistance in human pancreatic cancer cells.
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DOI：
10.4161/cbt.7.8.6300
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发表时间：
2008-08
影响因子：
3.6
通讯作者：
Goswami PC
中科院分区：
文献类型：
--
作者：
Fisher CJ;Goswami PC
近年来，细胞氧化还原环境作为细胞氧化应激反应的关键调节因子而受到广泛关注。细胞氧化还原环境是活性氧的产生与抗氧化酶的清除之间的平衡。我们研究了线粒体抗氧化酶活性调节人类胰腺癌细胞的放射抗性的假设。对载体对照和过表达锰超氧化物歧化酶 (MnSOD) 的人胰腺癌细胞进行照射，并检测细胞存活和 G2 检查点通路的激活。 6 Gy 伽玛射线照射后，MnSOD 活性的增加显着增加了细胞存活率 (p < 0.05)。与受辐射的载体对照相比，过表达 MnSOD 的受辐射细胞的 G2 细胞百分比也增加了 3-4 倍。此外，过表达 MnSOD 的受辐射细胞表现出磷酸化组蛋白 H2AX 蛋白水平损失增加。在受辐射的载体对照细胞中，辐射诱导的细胞周期蛋白 B1 蛋白水平的增加在受辐射的 MnSOD 过表达细胞中受到抑制。线粒体靶向过氧化氢酶的过度表达增加了受辐射细胞的存活率。这些结果支持这样的假设：线粒体抗氧化酶活性和线粒体产生的活性氧信号（超氧化物和过氧化氢）可以调节人类胰腺癌细胞中辐射诱导的 G2 检查点激活和放射抗性。
In recent years, cellular redox environment gained significant attention as a critical regulator of cellular responses to oxidative stress. Cellular redox environment is a balance between production of reactive oxygen species and their removal by antioxidant enzymes. We investigated the hypothesis that mitochondrial antioxidant enzyme activity regulates radioresistance in human pancreatic cancer cells. Vector-control and manganese superoxide dismutase (MnSOD) overexpressing human pancreatic cancer cells were irradiated and assayed for cell survival and activation of the G2-checkpoint pathway. Increased MnSOD activity significantly increased cell survival following irradiation with 6 Gy of gamma-radiation (p < 0.05). The MnSOD overexpressing irradiated cells also revealed 3–4 folds increase in the percentage of G2 cells compared to irradiated vector-control. Furthermore, MnSOD overexpressing irradiated cells exhibited increased loss of phosphorylated histone H2AX protein levels. The radiation-induced increase in cyclin B1 protein levels in irradiated vector-control cells was suppressed in irradiated MnSOD overexpressing cells. Mitochondria-targeted catalase overexpression increased the survival of irradiated cells. These results support the hypothesis that mitochondrial antioxidant enzyme activity and mitochondria-generated reactive oxygen species-signaling (superoxide and hydrogen peroxide) could regulate radiation-induced G2 checkpoint activation and radioresistance in human pancreatic cancer cells.
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影响因子：
56.9
作者：
Celeste, A;Petersen, S;Nussenzweig, A
通讯作者：
Nussenzweig, A
影响因子：
2.9
作者：
GRIFFITH, OW
通讯作者：
GRIFFITH, OW
影响因子：
2.6
作者：
NAGASAWA, H;KENG, P;LITTLE, JB
通讯作者：
LITTLE, JB
DOI：
10.1084/jem.103.5.653
发表时间：
1956-05-01
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
PUCK TT;MARCUS PI
通讯作者：
MARCUS PI
影响因子：
4.8
作者：
Savitsky, PA;Finkel, T
通讯作者：
Finkel, T