The presence of nitrite during UVA irradiation protects from apoptosis.
Nitrite occurs ubiquitously in biological fluids such as blood and sweat, representing an oxidation product of nitric oxide. Nitrite has been associated with a variety of adverse effects such as mutagenicity, carcinogenesis, and toxicity. In contrast, here we demonstrate that the presence of nitrite, but not nitrate, during irradiation of endothelial cells in culture exerts a potent and concentration-dependent protection against UVA-induced apoptotic cell death. Protection is half-maximal at a concentration of 3 mM, and complete rescue is observed at 10 mM. Nitrite-mediated protection is mediated via inhibition of lipid peroxidation in a similar manner as seen with butylated hydroxytoluene, a known inhibitor of lipid peroxidation. Interestingly, nitrite-mediated protection is completely abolished by coincubation with the NO scavenger cPTIO. Using electron paramagnetic resonance (EPR) spectroscopy or Faraday modulation spectroscopy, we directly prove UVA-induced NO formation in solutions containing nitrite. In conclusion, evidence is presented that nitrite represents a protective agent against UVA-induced apoptosis due to photodecomposition of nitrite and subsequent formation of NO.
Suschek
Christoph V
CV
Institute of Molecular Medicine, Research Group Immunobiology, Heinrich-Heine-University of Düsseldorf, 40225 Düsseldorf, Germany. suschek@uni-duesseldorf.de
Schroeder
Peter
P
Aust
Olivier
O
Sies
Helmut
H
Mahotka
Csaba
C
Horstjann
Markus
M
Ganser
Heiko
H
Mürtz
Manfred
M
Hering
Peter
P
Schnorr
Oliver
O
Kröncke
Klaus-Dietrich
KD
Kolb-Bachofen
Victoria
V
D017209:Apoptosis; D002478:Cells, Cultured; D003497:Cyclic N-Oxides / Q000494:pharmacology; D019610:Cytoprotection; D004305:Dose-Response Relationship, Drug; D004578:Electron Spin Resonance Spectroscopy; D004727:Endothelium / Q000166:cytology / Q000000981:diagnostic imaging / Q000187:drug effects / Q000378:metabolism; D016166:Free Radical Scavengers / Q000494:pharmacology; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D015227:Lipid Peroxidation / Q000187:drug effects; D008954:Models, Biological; D009569:Nitric Oxide / Q000378:metabolism; D009573:Nitrites / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000494:pharmacology*; D011859:Radiography; D014466:Ultraviolet Rays
D003497:Cyclic N-Oxides; D016166:Free Radical Scavengers; D007093:Imidazoles; D009573:Nitrites; C079391:2-phenyl-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide; D009569:Nitric Oxide