Autoimmune response to AGE modified human DNA: Implications in type 1 diabetes mellitus
Aims: Non-enzymatic glycation of DNA both in vivo and in vitro results in generation of free radicals, known as glycoxidation. Glycoxidation leads to structural perturbation of DNA resulting in generation of neo-antigenic epitopes having implication in autoimmune disorders like diabetes mellitus. In...
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| Format: | Article |
| Language: | English |
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Elsevier
2014-09-01
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| Series: | Journal of Clinical & Translational Endocrinology |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2214623714000167 |
| _version_ | 1819169254273974272 |
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| author | Saheem Ahmad Moin Uddin Safia Habib Uzma Shahab Khursheed Alam Asif Ali |
| author_facet | Saheem Ahmad Moin Uddin Safia Habib Uzma Shahab Khursheed Alam Asif Ali |
| author_sort | Saheem Ahmad |
| collection | DOAJ |
| description | Aims: Non-enzymatic glycation of DNA both in vivo and in vitro results in generation of free radicals, known as glycoxidation. Glycoxidation leads to structural perturbation of DNA resulting in generation of neo-antigenic epitopes having implication in autoimmune disorders like diabetes mellitus. In this study human placental DNA was glycated with methylglyoxal (MG) and lysine (Lys) in the presence of Cu2+ and its auto-antibody binding was probed in Type 1 diabetes patients.
Methods: Glycation was carried out by incubating DNA with MG, Lys and Cu2+ for 24 h at 37 °C. Carboxyethyl deoxyguanosine (CEdG) formed in glycation reaction was studied by LC-MS and the pathway for Amadori formation was studied by ESI-MS techniques. Furthermore, binding characteristics of auto-antibodies in diabetes patients were assessed by direct binding, competitive ELISA and band shift assay.
Results: DNA glycation with MG, Lys and Cu2+ results in the formation of CEdG (marker of DNA glycation) which was confirmed by LC-MS. The intermediate stages of glycation were confirmed by ESI-MS technique. Serum from diabetes patients exhibited enhanced binding and specificity for glycated DNA as compared to native form.
Conclusions: Glycation of DNA has resulted in structural perturbation causing generation of neo-antigenic epitopes thus recognizing auto-antibodies in diabetes. |
| first_indexed | 2024-12-22T19:16:34Z |
| format | Article |
| id | doaj.art-6e17560c53214f26a29f32881606a7f1 |
| institution | Directory Open Access Journal |
| issn | 2214-6237 |
| language | English |
| last_indexed | 2024-12-22T19:16:34Z |
| publishDate | 2014-09-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of Clinical & Translational Endocrinology |
| spelling | doaj.art-6e17560c53214f26a29f32881606a7f12022-12-21T18:15:30ZengElsevierJournal of Clinical & Translational Endocrinology2214-62372014-09-0113667210.1016/j.jcte.2014.05.002Autoimmune response to AGE modified human DNA: Implications in type 1 diabetes mellitusSaheem Ahmad0Moin Uddin1Safia Habib2Uzma Shahab3Khursheed Alam4Asif Ali5Department of Biochemistry, J.N. Medical College, Faculty of Medicine, Aligarh Muslim University, Aligarh, IndiaDepartment of Biochemistry, J.N. Medical College, Faculty of Medicine, Aligarh Muslim University, Aligarh, IndiaBiochemistry Section, Women's College, Aligarh Muslim University, Aligarh, IndiaDepartment of Biochemistry, J.N. Medical College, Faculty of Medicine, Aligarh Muslim University, Aligarh, IndiaDepartment of Biochemistry, J.N. Medical College, Faculty of Medicine, Aligarh Muslim University, Aligarh, IndiaDepartment of Biochemistry, J.N. Medical College, Faculty of Medicine, Aligarh Muslim University, Aligarh, IndiaAims: Non-enzymatic glycation of DNA both in vivo and in vitro results in generation of free radicals, known as glycoxidation. Glycoxidation leads to structural perturbation of DNA resulting in generation of neo-antigenic epitopes having implication in autoimmune disorders like diabetes mellitus. In this study human placental DNA was glycated with methylglyoxal (MG) and lysine (Lys) in the presence of Cu2+ and its auto-antibody binding was probed in Type 1 diabetes patients. Methods: Glycation was carried out by incubating DNA with MG, Lys and Cu2+ for 24 h at 37 °C. Carboxyethyl deoxyguanosine (CEdG) formed in glycation reaction was studied by LC-MS and the pathway for Amadori formation was studied by ESI-MS techniques. Furthermore, binding characteristics of auto-antibodies in diabetes patients were assessed by direct binding, competitive ELISA and band shift assay. Results: DNA glycation with MG, Lys and Cu2+ results in the formation of CEdG (marker of DNA glycation) which was confirmed by LC-MS. The intermediate stages of glycation were confirmed by ESI-MS technique. Serum from diabetes patients exhibited enhanced binding and specificity for glycated DNA as compared to native form. Conclusions: Glycation of DNA has resulted in structural perturbation causing generation of neo-antigenic epitopes thus recognizing auto-antibodies in diabetes.http://www.sciencedirect.com/science/article/pii/S2214623714000167DNAMethylGlyoxalGlycationAuto-antibodyDiabetes mellitus |
| spellingShingle | Saheem Ahmad Moin Uddin Safia Habib Uzma Shahab Khursheed Alam Asif Ali Autoimmune response to AGE modified human DNA: Implications in type 1 diabetes mellitus Journal of Clinical & Translational Endocrinology DNA MethylGlyoxal Glycation Auto-antibody Diabetes mellitus |
| title | Autoimmune response to AGE modified human DNA: Implications in type 1 diabetes mellitus |
| title_full | Autoimmune response to AGE modified human DNA: Implications in type 1 diabetes mellitus |
| title_fullStr | Autoimmune response to AGE modified human DNA: Implications in type 1 diabetes mellitus |
| title_full_unstemmed | Autoimmune response to AGE modified human DNA: Implications in type 1 diabetes mellitus |
| title_short | Autoimmune response to AGE modified human DNA: Implications in type 1 diabetes mellitus |
| title_sort | autoimmune response to age modified human dna implications in type 1 diabetes mellitus |
| topic | DNA MethylGlyoxal Glycation Auto-antibody Diabetes mellitus |
| url | http://www.sciencedirect.com/science/article/pii/S2214623714000167 |
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