FIP200蛋白对细胞氧化还原状态调控的研究

项目名称： FIP200蛋白对细胞氧化还原状态调控的研究

项目编号： No.31301174

项目类型： 青年科学基金项目

立项/批准年度： 2014

项目学科： 生物科学

项目作者： 王茜

作者单位： 上海交通大学

项目金额： 25万元

中文摘要： 细胞内适度的活性氧水平对维持细胞的稳恒性是非常重要的，任何氧化还原平衡的异常都可能与包括癌症在内的人类疾病发生有关。细胞内活性氧受到抗氧化系统的紧密调控。自噬是一条降解通路，细胞质内的组分会被隔离在双层膜围成的自噬体中并被运送到溶酶体中降解。活性氧可以诱导自噬，而自噬可以降低活性氧。 FIP200是一个多功能蛋白， FIP200-ULK1-ATG13复合物对自噬体的形成是必需的。活性氧会在FIP200缺失的胚胎造血干细胞的线粒体中积累，提示FIP200可能参与调控活性氧的产生。我们将研究FIP200是否可以调控活性氧的产生及其可能的机制。第一，我们将研究FIP200是否通过影响细胞内抗氧化系统调控活性氧；第二，我们将研究FIP200是否通过自噬调控活性氧。

中文关键词： 卵巢癌相关成纤维细胞；肿瘤干细胞；自噬；氧胁迫；活性氧

英文摘要： Proper intracellular reactive oxygen species (ROS) level is important for maintaining cellular homeostasis. Any perturbation of the redox balance may be related to the human diseases including cancer. The intracellular ROS level is tightly regulated by antioxidant system. Autophagy is a pathway by which cytosolic components are sequestered in a double-membrane-bound autophagosome and delivered to the lysosome for degradation. Autophagy is essential for survival, differentiation, development, and energy homeostasis. Accumulation of ROS induces autophagy, which, in turn serves to reduce ROS levels. FIP200 is a multifunctional protein, which exerts its functions through interacting with different proteins. FIP200-ULK1-ATG13 complex plays essential role for autophagosome formation. FIP200-null fetal hematopoietic stem cells exhibit increased ROS, indicating that FIP200 might regulate ROS production and cellular redox state. We will investigate whether FIP200 can regulate ROS production and the possible mechanisms. First, we will investigate whether FIP200 can regulate ROS production through regulating the antioxidant system. Second, we will investigate whether FIP200 can regulate ROS production through regulating autophagy.

英文关键词： ovarian cancer-associated fibroblast；cancer stem cells；autophagy；oxidative stress；reactive oxygen species