Serotonin-Cu(II)-mediated DNA cleavage: mechanism of copper binding by serotonin

被引:23
作者
Hadi, N
Malik, A
Azam, S
Khan, NU
Iqbal, J [1 ]
机构
[1] Aligarh Muslim Univ, Dept Biochem, Fac Life Sci, Aligarh 202002, Uttar Pradesh, India
[2] Aligarh Muslim Univ, Dept Chem, Fac Sci, Aligarh 202002, Uttar Pradesh, India
关键词
endogenous DNA damage; serotonin; Cu(II) reduction; quinone methide;
D O I
10.1016/S0887-2333(02)00083-8
中图分类号
R99 [毒物学(毒理学)];
学科分类号
100405 ;
摘要
It has been proposed that considerable DNA damage may be caused by endogenous metabolites produced during the body's normal metabolic processes. 5-hydroxytryptamine (serotonin) is an important neurotransmitter in brain and spinal cord. We have previously shown that serotonin induces oxidative cleavage of DNA strands in the presence of copper ions. In the present paper we have examined the mechanism of copper binding by serotonin using absorption spectroscopy, Cu(II)-mediated lipid peroxidation and by determining the oxidation of the serotonin molecule. Addition of increasing concentrations of Cu(II) to serotonin leads to a progressive enhancement in the absorption band and is accompanied by a shift towards a lower wavelength indicative of the formation of an oxidised species of serotonin. Studies with the structurally related molecules tryptophan and melatonin showed that only serotonin is able to reduce Cu(II) to Cu(I). Similarly, only serotonin was found to be able to abolish the copper-mediated peroxidation of mitochondria. These results suggested the involvement of the phenolic group in copper binding. Further, it was also shown that the binding of copper to serotonin leads to the formation of a quinone in the absence of molecular oxygen. Based on these results, a model has been proposed in which serotonin reduces two molar equivalents of Cu(II) to Cu(I) through a reaction involving two electron oxidation of the phenolic ring to a quinone methide. (C) 2002 Elsevier Science Ltd. All rights reserved.
引用
收藏
页码:669 / 674
页数:6
相关论文
共 18 条
  • [1] 1,10-Phenanthroline stimulates internucleosomal DNA fragmentation in isolated rat-liver nuclei by promoting the redox activity of endogenous copper ions
    Burkitt, MJ
    Milne, L
    Nicotera, P
    Orrenius, S
    [J]. BIOCHEMICAL JOURNAL, 1996, 313 : 163 - 169
  • [2] Characterization of an N-6-oxopropenyl-2'-deoxyadenosine adduct in malondialdehyde-modified DNA using liquid chromatography electrospray ionization tandem mass spectrometry
    Chaudhary, AK
    Reddy, GR
    Blair, IA
    Marnett, LJ
    [J]. CARCINOGENESIS, 1996, 17 (05) : 1167 - 1170
  • [3] DETECTION OF ENDOGENOUS MALONDIALDEHYDE-DEOXYGUANOSINE ADDUCTS IN HUMAN LIVER
    CHAUDHARY, AK
    NOKUBO, M
    REDDY, GR
    YEOLA, SN
    MORROW, JD
    BLAIR, IA
    MARNETT, LJ
    [J]. SCIENCE, 1994, 265 (5178) : 1580 - 1582
  • [4] DOPAMINE-DERIVED ALKALOIDS IN ALCOHOLISM AND IN PARKINSONS AND HUNTINGTONS DISEASES
    DOSTERT, P
    BENEDETTI, MS
    DORDAIN, G
    [J]. JOURNAL OF NEURAL TRANSMISSION, 1988, 74 (02) : 61 - 74
  • [5] PROTEIN-BOUND 3,4-DIHYDROXYPHENYLALANINE IS A MAJOR REDUCTANT FORMED DURING HYDROXYL RADICAL DAMAGE TO PROTEINS
    GIESEG, SP
    SIMPSON, JA
    CHARLTON, TS
    DUNCAN, MW
    DEAN, RT
    [J]. BIOCHEMISTRY, 1993, 32 (18) : 4780 - 4786
  • [6] Strand scission in DNA induced by 5-hydroxytryptamine (Serotonin) in the presence of copper ions
    Hadi, N
    Singh, S
    Ahmad, A
    Zaidi, R
    [J]. NEUROSCIENCE LETTERS, 2001, 308 (02) : 83 - 86
  • [7] WILSONS-DISEASE WITH CEREBRAL MANIFESTATION - MONITORING THERAPY BY CSF COPPER CONCENTRATION
    HARTARD, C
    WEISNER, B
    DIEU, C
    KUNZE, K
    [J]. JOURNAL OF NEUROLOGY, 1993, 241 (02) : 101 - 107
  • [8] STRAND SCISSION IN DNA INDUCED BY L-DOPA IN THE PRESENCE OF CU(II)
    HUSAIN, S
    HADI, SM
    [J]. FEBS LETTERS, 1995, 364 (01) : 75 - 78
  • [9] DNA strand scission and PC12 cell death induced by salsolinol and copper
    Kim, HJ
    Yoon, HR
    Washington, S
    Chang, II
    Oh, YJ
    Surh, YJ
    [J]. NEUROSCIENCE LETTERS, 1997, 238 (03) : 95 - 98
  • [10] The interaction of melatonin and its precursors with aluminium, cadmium, copper, iron, lead, and zinc: An adsorptive voltammetric study
    Limson, J
    Nyokong, T
    Daya, S
    [J]. JOURNAL OF PINEAL RESEARCH, 1998, 24 (01) : 15 - 21