HMGB1在白血病细胞凋亡和自噬调控机制的研究

项目名称： HMGB1在白血病细胞凋亡和自噬调控机制的研究

项目编号： No.81200378

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 医学一处

项目作者： 刘丽英

作者单位： 山东大学

项目金额： 23万元

中文摘要： 细胞凋亡和自噬机制的探讨是生命科学的研究热点。最近项目组在著名期刊《Leukemia》上报道HMGB1作为一种新型的促自噬蛋白参与了肿瘤耐药。根据最新发现凋亡与自噬密切相关，以及HMGB1负性调节白血病细胞凋亡的事实，申请者提出HMGB1参与调控白血病细胞凋亡和自噬的假说。针对上述假说，本项目拟采用各种先进的手段，在二种不同的自噬模型中（饥饿经典基础模型和化疗药物诱导的经典模型），从多个方面进一步深入系统的探讨HMGB1是如何调控凋亡和自噬的发生。其中，HMGB1是否通过Bcl-2或者其它凋亡途径影响自噬关键蛋白的剪切是研究重点。开展本项目可望揭示HMGB1在白血病细胞凋亡和自噬中的新机制，为HMGB1的功能研究开辟新的领域，为探求凋亡和自噬的关系提供新的实验线索，为临床白血病的防治提供新的思路。

中文关键词： 自噬；凋亡；高迁移率族蛋白-1；化疗耐药；白血病

英文摘要： The cross-regulation between antuohagy and apoptosis is still a hot spot in the field of life science.Recently，oue project team reported a novel pro-autophagy protein HMGB1 participating in tumor drug resistance published in a prestigous journal《Leukemia》.According to the close relationship between apoptosis and autophagy and that HMGB1 negatively regulates apoptosis of leukemia cells, the applicant puts forawrd the hypothesis that HMGB1 involved in regulating the autophagy and apoptosis in leukemia cells. In view of the above hypothesis, the project intends to explore a variety of advanced means and from several aspects to further discuss how HMGB1 is to regulate apoptosis and autophagy in two different autophagic models(classic starved and chemotherapy-induced models),of which the priority is whether HMGB1 influences the shear of autophagic key protein through Bcl-2 or other apoptosis pathways. This project is expected to reveal a new mechanism of HMGB1 in the regulation of apoptosis and autophagy, to expand a new field in the function of HMGB1,to provied new experimental clues in exploring the relationship between apoptosis and autophagy, and to supply new sights into the therapeutic interventions in leukemia.

英文关键词： autophagy；apoptosis；HMGB1；drug resistance；leukemia