Resveratrol activation of nitric oxide synthase in rabbit brain synaptosomes: singlet oxygen (1O2) formation as a causative factor of neurotoxicity.
In the present study it was shown that resveratrol (3,4,5-trihydroxystilbene), an efficient light-absorbing molecule, during its transition from trans to cis configuration under UV light, transfers its energy of excitation to triplet oxygen to produce singlet oxygen ((1)O(2)). This transition is prevented by Trolox, a quencher of singlet oxygen. In the presence of a stable amount of nitrosoglutathione, UV-irradiated resveratrol reacts with nitric oxide (NO) originating from the nitrosoglutathione to produce peroxynitrite (ONOO(-)). Beta-carotene, acting as a quencher of (1)O(2), prevents the transition of resveratrol from trans to cis. Beta-carotene also prevents DNA damage induced by the (1)O(2). NO synthase (NOS) activity in synaptosomes isolated from rabbit brain increased approximately three-fold by resveratrol and the NO released was converted to ONOO(-). Resveratrol increased the lipid fluidity of synaptosomal plasma membranes. These changes suggest that the incorporation of resveratrol into synaptosomal plasma membranes causes an up-regulation of NO synthase. On the other hand, the simultaneous ONOO(-) and (1)O(2) formation may cause disturbances in transmembrane signal transduction leading to neurotoxicity. The present study concerning the behavior of resveratrol with respect to its structure and potential prooxidant-antioxidant function provides important new clues as to the role of this fascinating molecule in pathophysiology.
Department of Experimental Physiology, University of Athens Medical School, Athens 11527, Greece.
Stelios
S
Fotiou
Despina
D
Fotiou
Anastasia
A
Alamanou
George
G
Deliconstantinos
D000818:Animals; D000975:Antioxidants / Q000032:analysis / Q000494:pharmacology* / Q000528:radiation effects; D002851:Chromatography, High Pressure Liquid; D004249:DNA Damage / Q000187:drug effects; D007425:Intracellular Membranes / Q000187:drug effects / Q000378:metabolism; D049449:Luminescence; D008560:Membrane Fluidity / Q000187:drug effects; D009566:Nitrates / Q000378:metabolism; D052248:Nitric Oxide Synthase Type I / Q000096:biosynthesis*; D018384:Oxidative Stress; D011817:Rabbits; D000077185:Resveratrol; D026422:S-Nitrosoglutathione / Q000378:metabolism; D026082:Singlet Oxygen / Q000378:metabolism*; D013267:Stilbenes / Q000032:analysis / Q000494:pharmacology* / Q000528:radiation effects; D013574:Synaptosomes / Q000187:drug effects* / Q000201:enzymology; D015854:Up-Regulation; D019207:beta Carotene / Q000494:pharmacology
D000975:Antioxidants; D009566:Nitrates; D013267:Stilbenes; D019207:beta Carotene; D026082:Singlet Oxygen; C039642:peroxynitric acid; D026422:S-Nitrosoglutathione; D052248:Nitric Oxide Synthase Type I; D000077185:Resveratrol