Peroxynitrite-modified DNA: a better antigen for systemic lupus erythematosus anti-DNA autoantibodies

被引:22
作者
Habib, S [1 ]
Ali, M [1 ]
Ali, R [1 ]
机构
[1] Aligarh Muslim Univ, Jawaharlal Nehru Med Coll, Dept Biochem, Aligarh 202002, Uttar Pradesh, India
关键词
anti-DNA autoantibody antigen; DNA damage; peroxynitrite; (ONOO-); peroxynitrite-modified DNA; systemic lupus erythematosus;
D O I
10.1042/BA20050156
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 [生物化学与分子生物学]; 081704 [应用化学];
摘要
Native human DNA was modified by ONOO- (peroxynitrite), generated by the synergistic action of sodium nitroprusside [Na2Fe(CN)(5)NO], an NO donor, and pyrogallol, a superoxide donor. The modifications were analysed by UV absorption characteristics, fluorescence emission transitions, nuclease S1 digestibility and melting-temperature studies. Modified DNA was found to be highly immunogenic, inducing high-titre immunogen-specific antibodies in experimental animals. A maximum of 85% inhibition of the antibody binding was observed in competition ELISA with immunogen as inhibitor. SLE (systemic lupus erythematosus) anti-DNA autoantibodies recognized modified DNA as a better antigen than the native analogue. Modification of native DNA by ONOO-, forming neo-epitopes on the molecule, may be one of the factors for the induction of the autoimmune response seen in SLE.
引用
收藏
页码:65 / 70
页数:6
相关论文
共 37 条
[1]
Role of ROS modified human DNA in the pathogenesis and etiology of cancer [J].
Abdi, S ;
Ali, A .
CANCER LETTERS, 1999, 142 (01) :1-9
[2]
Detection of oxidative DNA damage by a monoclonal antibody: role of lysyl residues in antigen binding [J].
Ahmad, J ;
Ashok, BT ;
Ali, R .
IMMUNOLOGY LETTERS, 1998, 62 (02) :87-92
[3]
Oxygen free radicals and systemic autoimmunity [J].
Ahsan, H ;
Ali, A ;
Ali, R .
CLINICAL AND EXPERIMENTAL IMMUNOLOGY, 2003, 131 (03) :398-404
[4]
ALAM K, 1992, BIOCHEM INT, V26, P597
[5]
Alam K, 1999, BIOCHEM MOL BIOL INT, V47, P881
[6]
ALBIRA JE, 1999, J IMMUNOL, V150, P5080
[7]
ANGARD E, 1997, LANCET, V343, P1199
[8]
REACTIVE OXYGEN SPECIES MODIFIED DNA FRAGMENTS OF VARYING SIZE ARE THE PREFERRED ANTIGEN FOR HUMAN ANTI-DNA AUTOANTIBODIES [J].
ARA, J ;
ALI, R .
IMMUNOLOGY LETTERS, 1992, 34 (03) :195-200
[9]
Antigenicity of poly(dA-dT)center dot poly(dA-dT) photocrosslinked with 8-methoxypsoralen [J].
Arif, Z ;
Ali, R .
ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS, 1996, 329 (02) :191-198
[10]
The aging paradox: free radical theory of aging [J].
Ashok, BT ;
Ali, R .
EXPERIMENTAL GERONTOLOGY, 1999, 34 (03) :293-303