[Methylglyoxal-induced apoptosis of endothelial cells].
Diabetic patients exhibit increased blood plasma levels of methylglyoxal (MG), a metabolite of glucose. Since MG generates advanced glycation end-products (AGEs) that disrupt the functions of such biomolecules as proteins, it is responsible for the progression and complications of diabetes. A functional disorder of the vascular endothelium may also contribute to the progression and complications of diabetes. In endothelial cells, MG is the major precursor for the formation of AGEs. In this study, we examined the effects of MG on vascular endothelial cells and found that it induced the apoptosis of bovine aortic endothelial cells (BAECs). MG induced the collapse of mitochondrial membrane potential, an index of apoptosis, and the elevation of caspase-3 activity, an apoptotic execution enzyme, leading to cell death. Flow cytometric analyses with annexin-V and propidium iodide double staining revealed that cells exposed to a lethal dose of MG displayed features characteristic of apoptosis. MG induced an increase in the level of intracellular reactive oxygen species (ROS) prior to induction of apoptosis. Taken together, these findings suggest that BAECs exposed to MG die by apoptosis due to the increase of intracellular ROS level.
Takahashi
Kyohei
K
Hokkaido Pharmaceutical University School of Pharmacy, Japan.
Tatsunami
Ryosuke
R
Tampo
Yoshiko
Y
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000378:metabolism; D002417:Cattle; D002478:Cells, Cultured; D048909:Diabetes Complications / Q000209:etiology; D003920:Diabetes Mellitus / Q000097:blood; D018450:Disease Progression; D042783:Endothelial Cells / Q000378:metabolism / Q000473:pathology*; D017127:Glycation End Products, Advanced / Q000378:metabolism; D011765:Pyruvaldehyde / Q000009:adverse effects* / Q000097:blood; D017382:Reactive Oxygen Species / Q000378:metabolism
D017127:Glycation End Products, Advanced; D017382:Reactive Oxygen Species; D011765:Pyruvaldehyde; D053148:Caspase 3