Antioxidants prevent high-D-glucose-enhanced endothelial Ca2+/cGMP response by scavenging superoxide anions.
Very recently we proposed that hyperactivity of endothelial Ca2+/cGMP signaling under hyperglycemic conditions is due to superoxide anion (O2-) release. The present study was designed to investigate changes in endothelial glutathione (GSH) levels in response to high D-glucose and possible prevention of the high-D-glucose-initiated changes in Ca2+/cGMP signal by antioxidants. Under hyperglycemic conditions, GSH content increased by 29% within 4 h. Co-incubation with 10 mM GSH during high-D-glucose treatment normalized the Ca2+/cGMP response associated with an increase in GSH content by 222%. Vitamin C (250 microM) markedly diminished the high-D-glucose-mediated hyperreactivity of endothelial Ca2+ entry (by 40%) and Ca2+ release (by 52%). Similar to GSH, co-incubation with vitamin E (alpha-tocopherol; 50 micrograms/ml) and probucol (50 microM) completely prevented the high-D-glucose-initiated hyperreactivity of the endothelial Ca2+/cGMP response. Vitamin E, probucol, GSH and vitamin C diminished the high-D-glucose-mediated O2- release by 78, 65, 89 and 46%, respectively. These data suggest that antioxidants prevent high-D-glucose-initiated changes in endothelial Ca2+/cGMP response by scavenging the overshoot of O2-.
Graier
W F
WF
Department of Medical Biochemistry, University of Graz, Austria. wolfgang.graier@kfunigraz.ac.at
Simecek
S
S
Hoebel
B G
BG
Wascher
T C
TC
Dittrich
P
P
Kostner
G M
GM
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D001205:Ascorbic Acid / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D002478:Cells, Cultured; D006152:Cyclic GMP / Q000096:biosynthesis*; D003600:Cytosol / Q000378:metabolism; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D016166:Free Radical Scavengers / Q000494:pharmacology; D005947:Glucose / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D005978:Glutathione / Q000378:metabolism / Q000494:pharmacology; D000960:Hypolipidemic Agents / Q000494:pharmacology; D009569:Nitric Oxide / Q000502:physiology; D011341:Probucol / Q000494:pharmacology; D013481:Superoxides / Q000378:metabolism*; D013552:Swine; D014810:Vitamin E / Q000494:pharmacology
D000975:Antioxidants; D016166:Free Radical Scavengers; D000960:Hypolipidemic Agents; D013481:Superoxides; D014810:Vitamin E; D009569:Nitric Oxide; D005978:Glutathione; D006152:Cyclic GMP; D005947:Glucose; D011341:Probucol; D001205:Ascorbic Acid; D002118:Calcium