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Taurine prevents high-glucose-induced human vascular endothelial cell apoptosis
Ist Teil von
American Journal of Physiology: Cell Physiology, 1999-12, Vol.277 (6), p.C1229-C1238
Ort / Verlag
United States
Erscheinungsjahr
1999
Quelle
Free E-Journal (出版社公開部分のみ)
Beschreibungen/Notizen
The Royal College of Surgeons in Ireland, Department of Surgery,
Beaumont Hospital, Dublin, Ireland
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.
diabetes; hyperglycemia; reactive oxygen species; intracellular
calcium; cell necrosis