Ashraf Jalaluddin M, Shahab Uzma, Tabrez Shams, Lee Eun Ju, Choi Inho, Aslam Yusuf Mohd, Ahmad Saheem
School of Biotechnology, Yeungnam University, Gyeongsan, Republic of Korea.
Department of Biochemistry, King George's Medical University, Lucknow, U.P., India.
Cell Biochem Biophys. 2016 Mar;74(1):67-77. doi: 10.1007/s12013-015-0713-6.
The non-enzymatic glycation reaction results in the generation of free radicals which play an important role in the pathophysiology of aging, diabetes, and cancer. 3-Deoxyglucosone (3-DG) is a dicarbonyl species which may lead to the formation of advanced glycation end products (AGEs). 3-DG also reacts with free amino group of nucleic acids resulting in the formation of DNA-AGEs. While the establishment of nucleoside AGEs has been revealed before, no extensive studies have been done to probe the role of 3-DG in the generation of immunogenicity and induction of cancer auto-antibodies. In this study, we report the immunogenicity of AGEs formed by 3-DG-Arg-Fe(3+) system. Spectroscopic analysis and melting temperature studies suggest structural perturbations in the DNA as a result of modification. Immunogenicity of native and 3-DG-Arg-Fe(3+) DNA was probed in female rabbits. The modified DNA was highly immunogenic eliciting high-titer immunogen-specific antibodies, while the unmodified form was almost non-immunogenic. We also report the presence of auto-antibodies against 3-DG-Arg-Fe(3+)-modified DNA in the sera of patients with different types of cancers. The glycoxidative lesions were also detected in the lymphocyte DNA isolated from selected cancer patients. The results show structural perturbations in 3-DG-Arg-Fe(3+)-DNA generating new epitopes that render the molecule immunogenic.
非酶糖基化反应会产生自由基，这些自由基在衰老、糖尿病和癌症的病理生理学中起着重要作用。3-脱氧葡萄糖酮（3-DG）是一种二羰基化合物，可能导致晚期糖基化终产物（AGEs）的形成。3-DG还与核酸的游离氨基反应，导致DNA-AGEs的形成。虽然之前已经揭示了核苷AGEs的形成，但尚未进行广泛研究来探究3-DG在免疫原性产生和癌症自身抗体诱导中的作用。在本研究中，我们报告了由3-DG-精氨酸-Fe(3+)系统形成的AGEs的免疫原性。光谱分析和熔解温度研究表明，修饰导致DNA结构发生扰动。在雌性兔子中检测了天然DNA和3-DG-精氨酸-Fe(3+)修饰DNA的免疫原性。修饰后的DNA具有高度免疫原性，可引发高滴度的免疫原特异性抗体，而未修饰的形式几乎没有免疫原性。我们还报告了不同类型癌症患者血清中存在针对3-DG-精氨酸-Fe(3+)修饰DNA的自身抗体。在从选定癌症患者分离的淋巴细胞DNA中也检测到了糖氧化损伤。结果表明，3-DG-精氨酸-Fe(3+)-DNA中的结构扰动产生了新的表位，使该分子具有免疫原性。
