Strand scission in DNA induced by 5-hydroxytryptamine (serotonin) in the presence of copper ions.
It has been proposed that considerable DNA damage may be caused by endogenous metabolites produced during the body's normal metabolic processes. Several metabolites including L-3,4-dihydroxyphenylalanine and dopamine have been previously shown to lead to oxidative DNA breakage in the presence of copper ions. 5-hydroxytryptamine or serotonin is an important neurotransmitter in brain and spinal cord and is involved in the control of sleep and consciousness, aggression and mood. In this paper we show that serotonin is also capable of causing strand cleavage in DNA in the presence of Cu(II) through an oxidative mechanism. Serotonin reduces Cu(II) to Cu(I) which is accompanied by the generation of hydroxyl radical. Spectroscopic data indicate that serotonin is able to bind to DNA and copper ions. Relative DNA cleavage efficiency and copper binding ability of serotonin and structurally related molecules tryptophan and melatonin indicates that the phenolic group in serotonin is required for strand cleavage activity.
Hadi
N
N
Department of Biochemistry, Faculty of Life Sciences, AMU, Aligarh 202 002, India. smhadi@del6.vsnl.net.in
Singh
S
S
Ahmad
A
A
Zaidi
R
R
D000818:Animals; D002417:Cattle; D002490:Central Nervous System / Q000378:metabolism*; D003300:Copper / Q000378:metabolism* / Q000494:pharmacology; D004247:DNA / Q000187:drug effects / Q000378:metabolism*; D004249:DNA Damage / Q000502:physiology*; D017665:Hydroxyl Radical / Q000378:metabolism*; D008550:Melatonin / Q000378:metabolism / Q000494:pharmacology; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000502:physiology*; D010957:Plasmids / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D012701:Serotonin / Q000378:metabolism* / Q000494:pharmacology; D015719:Single-Strand Specific DNA and RNA Endonucleases / Q000187:drug effects / Q000378:metabolism; D013950:Thymus Gland / Q000187:drug effects / Q000378:metabolism; D014364:Tryptophan / Q000378:metabolism / Q000494:pharmacology
D012701:Serotonin; D017665:Hydroxyl Radical; D003300:Copper; D014364:Tryptophan; D004247:DNA; D015719:Single-Strand Specific DNA and RNA Endonucleases; D008550:Melatonin