Taurine prevents high-glucose-induced human vascular endothelial cell apoptosis.
Elevated blood glucose in uncontrolled diabetes is causally correlated with diabetic microangiopathy. Hyperglycemia-triggered accelerated endothelial cell apoptosis is a critical event in the process of diabetes-associated microvascular disease. The conditionally semiessential amino acid taurine has been previously shown to protect against human endothelial cell apoptosis. Therefore, this study was designed to investigate the role of taurine in the prevention of high-glucose-mediated cell apoptosis in human umbilical vein endothelial cells (HUVEC) and the mechanisms involved. Exposure of HUVEC to 30 mM glucose for 48 h (short-term) and 14 days (long-term) resulted in a significant increase in apoptosis, compared with normal glucose (5.5 mM; P < 0.05). High-glucose-induced DNA fragmentation preferentially occurred in the S phase cells. Mannitol (as osmotic control) at 30 mM failed to induce HUVEC apoptosis. Taurine prevented high-glucose-induced HUVEC apoptosis, which correlates with taurine attenuation of high-glucose-mediated increased intracellular reactive oxygen species (ROS) formation and elevated intracellular Ca(2+) concentration ([Ca(2+)](i)) level. Antioxidants, DMSO, N-acetyl cysteine, and glutathione, only partly attenuated high-glucose-induced HUVEC apoptosis. Glucose at 30 mM did not cause HUVEC necrosis. However, both glucose and mannitol at 60 mM caused HUVEC necrosis as represented by increased lactate dehydrogenase release and cell lysis. Taurine failed to prevent hyperosmolarity-induced cell necrosis. These results demonstrate that taurine attenuates hyperglycemia-induced HUVEC apoptosis through ROS inhibition and [Ca(2+)](i) stabilization and suggest that taurine may exert a beneficial effect in preventing diabetes-associated microangiopathy.
Wu
Q D
QD
The Royal College of Surgeons in Ireland, Department of Surgery, Beaumont Hospital, Dublin, Ireland.
Wang
J H
JH
Fennessy
F
F
Redmond
H P
HP
Bouchier-Hayes
D
D
D000975:Antioxidants / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D018053:Arsenites / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D053938:DNA Fragmentation / Q000187:drug effects; D003925:Diabetic Angiopathies / Q000188:drug therapy / Q000378:metabolism; D004234:Diuretics, Osmotic / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005947:Glucose / Q000494:pharmacology*; D006706:Homeostasis / Q000187:drug effects; D006801:Humans; D007476:Ionophores / Q000494:pharmacology; D008353:Mannitol / Q000494:pharmacology; D009336:Necrosis; D009994:Osmolar Concentration; D017382:Reactive Oxygen Species / Q000378:metabolism; D017670:Sodium Compounds / Q000494:pharmacology; D013654:Taurine / Q000494:pharmacology*; D014471:Umbilical Veins / Q000166:cytology
D000975:Antioxidants; D018053:Arsenites; D004234:Diuretics, Osmotic; D004791:Enzyme Inhibitors; D007476:Ionophores; D017382:Reactive Oxygen Species; D017670:Sodium Compounds; D013654:Taurine; D008353:Mannitol; C017947:sodium arsenite; D005947:Glucose; D002118:Calcium