Drp-1基因在高糖诱导胰岛β细胞凋亡中的作用

The effect of dynamin-related protein 1 on high glucose-induced pancreatic β cell apoptosis

目的探讨动力相关蛋白-1(Drp-1)基因表达对高糖诱导胰岛β细胞凋亡的影响。方法高糖条件下,观察可诱导表达野生型Drp-1(Drp-1WT)基因和突变型Drp-1(Drp-1K38A)基因的大鼠胰岛β细胞凋亡情况。结果强力土霉素(Dox)可诱导胰岛β细胞Drp-1基因表达,并且Drp-1的表达与Dox之间存在明显的剂量和时间依赖关系。在高糖条件下,Drp-1WT基因高表达细胞的凋亡明显增多(39.1%),而Drp-1K38A高表达细胞的凋亡未见明显增加(8.9%)。并且高糖条件下,Dox诱导后的Drp-1WT细胞中可见线粒体分裂和细胞色素c释放,细胞中caspase 3活性升高,ROS产生增加,而这些变化在高表达Drp-1K38A的细胞中不明显。结论 Drp-1基因参与高糖诱导的胰岛β细胞凋亡。

Objective To explore the effect of dynamin-related protein 1（Drp-1） on high glucose-induced β cell apoptosis. Methods The inducible expression of either wild-type Drp-1（Drp-1WT） or its dominant-negative mutant （Drp-1K38A） in β cell lines were used to investigate the effects of expression of Drp-1 on high glucose-induced pancreatic β cell apoptosis and to probe the mechanisms of apoptosis. Results Both Drp-1WT and Drp-1K38A proteins of β cell lines were induced by doxycycline in dose and time dependent manner.In response to high glucose,the apoptosis was increased in Drp-1WT cells（39.1%）,but not in Drp-1K38A cells（8.9%） after induction of Dox（P〈0.05）.Glucose-evoked mitochondrial fission,release of cytochrome C,the increase of the activity of caspase3 and generation of ROS were found in Drp-1WT cells,but not in Drp-1K38A cells after Dox induction. Conclusion Drp-1 is implicated in β cell glucotoxicity and apoptosis.