C. Kimura et al., ACUTE GLUCOSE OVERLOAD ABOLISHES CA2-CELLS FROM BOVINE AORTA - A POSSIBLE ROLE OF SUPEROXIDE ANION( OSCILLATION IN CULTURED ENDOTHELIAL), Circulation research, 82(6), 1998, pp. 677-685
Effects of acute glucose overload on [Ca2+](i) were investigated in cu
ltured endothelial cells from bovine aorta. Application of 0.1 mu mol/
L ATP elicited an oscillatory increase in [Ca2+](i) (Ca2+ oscillation)
in Krebs solution containing 11.5 mmol/L glucose. The frequency of Ca
2+ oscillation induced by ATP increased in a concentration-dependent m
anner, ranging between 0.03 and 1 mu mol/L. When cells were preincubat
ed with 23 mmol/L glucose-containing Krebs solution (high glucose solu
tion) for 3 hours, 0.1 mu mol/L ATP failed to induce Ca2+ oscillation
but evoked only a phasic followed by sustained increase in [Ca2+](i).
Application of a higher concentration of ATP (10 mu mol/L) evoked a tr
ansient increase in [Ca2+](i) both in control and high glucose-treated
cells. However, the falling phase of [Ca2+](i) was prolonged in high
glucose-treated cells, Thapsigargin (1 mu mol/L), an inhibitor of endo
plasmic Ca2+-ATPase, induced a transient followed by a sustained incre
ase in [Ca2+](i) in control cells. Preincubation with high glucose sol
ution increased the rate of rise of the thapsigargin-induced increase
in [Ca2+](i) and abolished the sustained increase, suggesting that glu
cose overload accelerates Ca2+ leak from intracellular store sites and
impairs Ca2+ release-activated Ca2+ entry. We found that all of the g
lucose overload-induced changes in Ca2+ mobilization could be mimicked
by xanthine with xanthine oxidase and abolished by superoxide dismuta
se. These results indicate that acute glucose overload accumulates sup
eroxide anion in bovine aortic endothelial cells, thereby diminishing
ATP-induced Ca2+ oscillation through the impairment of Ca2+ homeostasi
s.