Suppression of nitric oxide toxicity in islet cells by alpha-tocopherol.
We show here that preincubation of pancreatic islet cells with alpha-tocopherol significantly improves their resistance to toxic doses of nitric oxide (NO). No protection was afforded by other antioxidants such as vitamin C or glutathione-monoethyl ester. The pathway of NO induced islet cell death involves DNA damage and excessive activation of poly(ADP-ribose)polymerase leading to irreversible depletion of intracellular NAD+. alpha-Tocopherol was found to interfere at early steps of this pathway, by preventing the occurrence of DNA strand breaks. This indicates that alpha-tocopherol directly interacts with NO or its reactive intermediates. We conclude that alpha-tocopherol is not only part of the cellular defence system against oxygen radicals but also protects eukaryotic cells from NO toxicity.
Burkart
V
V
Diabetes-Forschungsinstitut, Heinrich-Heine-Universität Düsseldorf, Germany.
Gross-Eick
A
A
Bellmann
K
K
Radons
J
J
Kolb
H
H
D000818:Animals; D001205:Ascorbic Acid / Q000494:pharmacology; D016923:Cell Death / Q000187:drug effects; D004249:DNA Damage / Q000187:drug effects; D004789:Enzyme Activation / Q000187:drug effects; D005978:Glutathione / Q000031:analogs & derivatives / Q000494:pharmacology; D007515:Islets of Langerhans / Q000166:cytology / Q000187:drug effects*; D007700:Kinetics; D009569:Nitric Oxide / Q000633:toxicity*; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D014810:Vitamin E / Q000494:pharmacology*
D014810:Vitamin E; D009569:Nitric Oxide; C042431:S-ethyl glutathione; D011065:Poly(ADP-ribose) Polymerases; D005978:Glutathione; D001205:Ascorbic Acid