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 mi
crovascular 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 t
he prevention of high-glucose-mediated cell apoptosis in human umbilical ve
in 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 indu
ce HUVEC apoptosis. Taurine prevented high-glucose-induced HUVEC apoptosis,
which correlates with taurine attenuation of high-glucose-mediated increas
ed intracellular reactive oxygen species (ROS) formation and elevated intra
cellular Ca2+ concentration ([Ca2+](i)) level. Antioxidants, DMSO, N-acetyl
cysteine, and glutathione, only partly attenuated high-glucose-induced HUV
EC apoptosis. Glucose at 30 mM did not cause HUVEC necrosis. However, both
glucose and mannitol at 60 mM caused HUVEC necrosis as represented by incre
ased lactate dehydrogenase release and cell lysis. Taurine failed to preven
t hyperosmolarity-induced cell necrosis. These results demonstrate that tau
rine attenuates hyperglycemia-induced HUVEC apoptosis through ROS inhibitio
n and [Ca2+](i) stabilization and suggest that taurine may exert a benefici
al effect in preventing diabetes-associated microangiopathy.