Department of Anaesthesiology, Fudan University Shanghai Cancer Centre, Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.
Department of Anaesthesiology, Shanghai Medical College, Fudan University, Shanghai, China.
Acta Biochim Biophys Sin (Shanghai). 2018 Jul 1;50(7):635-642. doi: 10.1093/abbs/gmy051.
Hyperglycemic memory occurs in diabetic cardiovascular complications, but the underlying mechanism remains to be elucidated. Although the depletion of SET8 leads to increased mitochondrial oxidative stress via increasing cellular reactive oxygen species (ROS) production, the role of SET8 in hyperglycemic memory-induced mitochondrial dysfunction is not well understood. Here, we investigated the role of SET8 in this setting. Our results showed that high glucose-induced vascular inflammation, ROS production and apoptosis remained at high levels even when glucose returned to normal level. Elevated glucose reduced SET8 expression, which also remained at low level after returning to normoglycemia. SET8 overexpression protected cells from elevated glucose and hyperglycemic memory-induced endothelial injury by blocking ROS accumulation, attenuating vascular inflammation, and restoring nitric oxide production. Thus, our results suggest that SET8 may be a key mediator in hyperglycemic memory.
高血糖记忆发生在糖尿病心血管并发症中，但潜在机制仍有待阐明。尽管 SET8 的耗竭会通过增加细胞内活性氧 (ROS) 的产生导致线粒体氧化应激增加，但 SET8 在高血糖记忆诱导的线粒体功能障碍中的作用尚不清楚。在这里，我们研究了 SET8 在这种情况下的作用。我们的结果表明，即使葡萄糖恢复到正常水平，高葡萄糖诱导的血管炎症、ROS 产生和细胞凋亡仍保持在较高水平。升高的葡萄糖降低了 SET8 的表达，即使在恢复正常血糖后，SET8 的表达仍保持在较低水平。SET8 的过表达通过阻止 ROS 积累、减轻血管炎症和恢复一氧化氮产生来保护细胞免受高葡萄糖和高血糖记忆诱导的内皮损伤。因此，我们的结果表明，SET8 可能是高血糖记忆的关键介质。
