Immunological studies on DNA‐lysine photoadduct

Islam, Najmul; Ali, Rashid

doi:10.1080/15216549800202842

Cited by 5 publications

(6 citation statements)

References 9 publications

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“…It has been postulated that immune response against host antigens could result from genetic predisposition, exaggerated random B cell activity, cross‐reactivity between foreign and host antigens. The foreign antigens arise as a consequence of infection, inflammation, drug administration, environmental factors, free radicals [29–35] and scores of other modifying agents. ROS have gained considerable interest in recent years as plausible causative agents in the pathogenesis of several human degenerative diseases [36].…”

Section: Systemic Autoimmune Disordersmentioning

confidence: 99%

Oxygen free radicals and systemic autoimmunity

Ahsan¹,

Ali²,

Ali

2003

Clinical and Experimental Immunology

220

144

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SUMMARYReactive oxygen species generated during various metabolic and biochemical reactions have multifarious effects that include oxidative damage to DNA leading to various human degenerative and autoimmune diseases. The highly reactive hydroxy radical (·OH) can interact with chromatin and result in a wide range of sugar and base-derived products, DNA-protein cross-links and strand breaks. Studies from our laboratory have demonstrated that after modification the DNA becomes highly immunogenic and the induced antibodies exhibit variable antigen-binding characteristics. Systemic lupus erythematosus, a prototype autoimmune disease, is characterized by the presence of autoantibodies to multiple nuclear antigens. The detection of 8-hydroxyguanosine in the immune complex derived DNA of systemic lupus erythematosus patients reinforces the evidence that reactive oxygen species may be involved in its pathogenesis. Increased apoptosis and decreased clearance of apoptotic cells as observed in systemic lupus erythematosus (SLE) might well be a contributory factor in systemic autoimmunity. Clinically, titres of autoantibodies are closely related to the degree of renal inflammation. Anti-DNA antibodies may combine with circulating antigen and contribute to the deposition of immune complexes in renal glomeruli.

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Section: Systemic Autoimmune Disordersmentioning

confidence: 99%

Oxygen free radicals and systemic autoimmunity

Ahsan¹,

Ali²,

Ali

2003

Clinical and Experimental Immunology

220

144

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“…20 Therefore, the DNA-arginine photoadduct and modified photoadduct could have important implications in various pathophysiological conditions such as toxicology, carcinogenesis, and autoimmune phenomena. [21][22][23][24] …”

Section: Discussionmentioning

confidence: 99%

Analysis of Human DNA-Arginine Photoadduct Modified with Peroxynitrite

Ahmad

Yadav²,

Chaudhary³

et al. 2012

Nucleosides, Nucleotides and Nucleic Acids

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The aim of the study is the biochemical characterization of human DNA modified with arginine and peroxynitrite. In the present study, DNA was isolated from human blood cells and its adduct was formed with one of the amino acid, arginine. The DNA-arginine adduct was then modified with peroxynitrite, a reactive nitrogen species. The modified DNA adduct was characterized by ultraviolet (UV) absorption spectroscopy, thermal melting profile, and electrophoresis studies. UV spectroscopic analysis of the photoadduct showed hyperchromicity, indicating the formation of single-strand breaks and photomodification. Thermal denaturation studies of DNA-arginine adduct and peroxynitrite-modified adduct showed a decrease in the temperature (T(m)) value by 4.5°C and an increase in the T(m) of 8°C, respectively. Peroxynitrite modification is evident by an increase in the T(m) value and a change in the migration pattern of native and modified photoadducts on agarose gel electrophoresis. The DNA-arginine and peroxynitrite-modified photoadducts could have important implications in various pathophysiological and immunopathological conditions.

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“…We have investigated the photochemical addition of lysine to native DNA in view of its potential importance in the photo-cross-linking of histones to DNA in chromatin. The C-2 carbon atom of thymine in DNA undergoes a covalent photoaddition reaction with the ε-amino group of lysine on UV irradiation to form a DNA-lysine photoconjugate or photoadduct (57). The UV spectroscopic analysis of the DNA-lysine photoadduct showed hyperchromism, indicating either the formation of single-stranded breaks in DNA or "breathing" of a double-stranded polymer at the site of lysine conjugation.…”

Section: Cellular Biochemistry and Pathologymentioning

confidence: 99%

“…Lysine is an amino acid of particular interest as a potential participant in DNAprotein photo-cross-linking. Nearly 60% of thymine and cytosine bases in DNA are modified due to lysine photoaddition and approximately every helical turn of DNA contains one lysine molecule in the photobound state (57). It appears to enhance the antigenicity of the DNAlysine adduct, suggesting possible roles of peroxynitrite-induced neoepitopes in damaged DNA in the production of autoantibodies in cancer patients (58).…”

Section: Cellular Biochemistry and Pathologymentioning

confidence: 99%

“…It has been postulated that the immune response against host antigens could be due to genetic predisposition, exaggerated B cell activity, cross-reactivity between foreign and host antigens, etc. The foreign antigens arise as a consequence of infection, inflammation, drug administration, environmental factors, free radicals, etc (57,61). It has been established that not only oxygen but nitrogen free radicals play an important role in the pathogenesis of several human diseases.…”

Section: Autoimmune Phenomenonmentioning

confidence: 99%

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