Effect of ghrelin on human endothelial cells apoptosis induced by high glucose.
Endothelial dysfunction is thought to be a major cause of vascular complications in diabetes. Our research shows that ghrelin attenuates high glucose-induced apoptosis in cultured human umbilical vein endothelial cells (ECV-304). Exposure to glucose (33.3mM) for 72 h caused a significant increase in apoptosis, as evaluated by TUNEL and flow cytometry, but pretreatment of ghrelin (10(-7)M) eliminated high glucose-induced apoptosis in ECV-304. Ghrelin also prevented the induction of caspase-3 activation, in cells incubated with glucose (33.3 mM). Exposure of cells to ghrelin (10(-7)M) caused rapid activation of Akt. PI3K inhibitor, LY294002 attenuated ghrelin's inhibitory effect on caspase-3 activity. Ghrelin protected endothelial cells from high glucose by inhibiting reactive oxygen species (ROS) generation. Results of our study indicate that ghrelin inhibits both high glucose-induced apoptosis via PI3K/Akt pathway and ROS production in ECV-304. This peptide may have potential in preventing diabetic complications, especially in obese patients.
Zhao
Hong
H
Department of Endocrinology, First Hospital of China Medical University, ShenYang 110001, China.
Liu
GuoLiang
G
Wang
QiuYue
Q
Ding
LiYing
L
Cai
Hui
H
Jiang
HaiHong
H
Xin
ZhongQiu
Z
D017209:Apoptosis; D053148:Caspase 3 / Q000378:metabolism; D002478:Cells, Cultured; D003920:Diabetes Mellitus / Q000378:metabolism; D004730:Endothelium, Vascular / Q000166:cytology* / Q000473:pathology; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D054439:Ghrelin; D005947:Glucose / Q000378:metabolism*; D006801:Humans; D020287:In Situ Nick-End Labeling; D009765:Obesity / Q000378:metabolism; D036361:Peptide Hormones / Q000378:metabolism*; D010455:Peptides / Q000737:chemistry; D017382:Reactive Oxygen Species; D014471:Umbilical Veins / Q000166:cytology / Q000473:pathology
D004791:Enzyme Inhibitors; D054439:Ghrelin; D036361:Peptide Hormones; D010455:Peptides; D017382:Reactive Oxygen Species; D053148:Caspase 3; D005947:Glucose