SET8调控HIF-1α/HK2→糖酵解功能轴参与高血糖诱导血管内皮细胞氧化应激的机制研究

Hyperglycemia is common in perioperative and ICU, which usually indicates a poor prognosis. Hyperglycemia reprograms glucose metabolism in vascular endothelial cells, and elevates ROS levels causing oxidative stress. The mechanisms of active glycolytic and ROS accumulation caused by hyperglycemia are still unknown. Our previous research found: 1. Hyperglycemia improved glycolysis and ROS level in vascular endothelial cells and induced oxidative stress; 2.SET8 mutation correlated to the glycolysis and ROS accumulation in Hyperglycemia; 3.HIF-1α promoted glycolysis and ROS production via HK2 in vascular endothelial cells; 4. SET8 regulated HIF-1α gene expression epigenetically. Therefore, the hypothesis is that SET8 epigenetic regulates HIF-1α/HK2→glycolysis function axis involved in Hyperglycemia-induced endothelial cell oxidative stress. In order to prove the hypothesis, we plan to conduct the following studies: 1. to verify the epigenetic modification of SET8 on HIF-1α; 2.to investigate the pathway of SET8/HIF-1α / HK2; 3. to elucidate the impact of the pathway on glycolysis and ROS; 4.to clarify the pathway in glycolysis and oxidative stress in vitro and in vivo. Therefore, the project will provide new ideas for clinical hyperglycemia vascular protection.

高糖血症是围术期和ICU中常见的并发症，与患者预后密切相关。高糖血症中血管内皮细胞糖代谢重编程，ROS水平升高，引起氧化应激。高血糖引起糖酵解活跃与ROS堆积的分子调控机制仍缺乏研究。我们前期研究发现：1.活跃的糖酵解提高内皮细胞ROS水平，诱导氧化应激；2.SET8蛋白与高糖环境糖酵解和ROS水平有密切关系；3.HIF-1α/HK2促进内皮细胞糖酵解和ROS的生成；4.SET8表观调控HIF-1α基因表达。因此提出假说：SET8表观调控HIF-1α/HK2→糖酵解功能轴参与高血糖诱导的血管内皮细胞氧化应激。本项目拟展开如下研究：1.探索SET8表观调控HIF-1α基因的分子机制；2.分析SET8、HIF-1α与HK2的关系，进行细胞分子生物学验证；3.阐明此通路对糖酵解及ROS水平的影响；4.通过体内外实验干预此信号通路，明确其对氧化应激的影响，为临床高糖血症血管保护提供新的思路。

高糖血症常见于围术期和ICU，与患者预后密切相关。高糖血症中内皮细胞糖代谢重编程，ROS水平升高，引起氧化应激。高血糖引起活跃的糖酵解与ROS堆积的分子调控机制仍缺乏研究。本课题研究发现：1.活跃的糖酵解提高内皮细胞ROS水平，诱导氧化应激；2.SET8蛋白与高糖环境糖酵解和ROS水平有密切关系；3.HIF-1α/HK2促进内皮细胞糖酵解和ROS的生成；4.SET8表观调控HIF-1α基因表达。验证假说：SET8表观调控HIF-1α/HK2→糖酵解功能轴参与高血糖诱导的血管内皮细胞氧化应激。本项目拟展开如下研究：1.探索SET8表观调控HIF-1α基因的分子机制；2.分析SET8、HIF-1α与HK2的关系，进行细胞分子生物学验证；3.阐明此通路对糖酵解及ROS水平的影响；4.通过体内外实验干预此信号通路，明确其对氧化应激的影响，为临床高糖血症血管保护提供新的思路。

内容获取失败，请点击重试