General Research Article

不同癌症患者金属催化氧化损伤DNA自身抗体的产生

卷 31, 期 5, 2024

发表于: 09 June, 2023

页: [640 - 648] 页: 9

弟呕挨: 10.2174/0929867330666230503143133

价格: $65

conference banner
摘要

背景:自由基是一种不稳定的高活性物质,存在于体内和体外。自由基被标记为由代谢和内源性氧燃烧形成的电子饥渴分子。它们在细胞内运输,扰乱分子的排列,引发细胞损伤。羟基自由基(•OH)是一种高活性自由基,对其附近的生物分子具有损伤作用。 方法:在本研究中,DNA被通过芬顿反应产生的羟基自由基修饰。用紫外可见光谱和荧光光谱对氧化修饰DNA (Ox-DNA)进行了表征。热变性是为了揭示修饰DNA对热的敏感性。通过直接结合ELISA检测癌症患者血清中Ox-DNA自身抗体的存在,也证实了Ox-DNA的作用。同时用抑制酶联免疫吸附试验检测自身抗体的特异性。 结果:在生物物理表征中,与天然DNA类似物相比,报告了Ox-DNA的高染度增加和荧光强度的相对降低。一项热变性研究表明,与天然构象相比,Ox-DNA对热非常敏感。直接结合酶联免疫吸附试验显示,从癌症患者血清中分离出针对Ox-DNA的自身抗体。生成的Ox-DNA自身抗体对膀胱癌、头颈癌和肺癌具有高度特异性,血清抗体和IgG抗体的抑制ELISA进一步证实了这一点。 结论:DNA分子上产生的新表位被免疫系统识别为非自身,从而导致癌症患者形成自身抗体。因此,我们的研究证实了氧化应激在DNA的结构扰动中起作用,使其具有免疫原性。

关键词: 羟基自由基(•OH),芬顿反应,新表位,自身抗体,癌症,受损DNA。

[1]
Halliwell, B. Protection against oxidants in biological systems. The superoxide theory of oxygen toxicity. Biol. Med., 1989, 86-123.
[2]
Zeng, W.; Zhang, H.; Yuan, X.; Chen, T.; Pei, Z.; Ji, X. Two-dimensional nanomaterial-based catalytic medicine: Theories, advanced catalyst and system design. Adv. Drug Deliv. Rev., 2022, 184, 114241.
[http://dx.doi.org/10.1016/j.addr.2022.114241] [PMID: 35367308]
[3]
Rafi, Z.; Alouffi, S.; Khan, M.S.; Ahmad, S. 2′-Deoxyribose mediated glycation leads to alterations in BSA structure via generation of carbonyl species. Curr. Protein Pept. Sci., 2020, 21(9), 924-935.
[http://dx.doi.org/10.2174/1389203721666200213104446] [PMID: 32053073]
[4]
Ahmad, S.; Rehman, S.; Alsulimani, A.; Al-shaghdali, K.; Khan, M. Y. Non-enzymatic glycosylation of isolated human Immunoglobulin-G by D-Ribose. Cell Biochem. Funct., 2022, 40(5), 526-534.
[http://dx.doi.org/10.1002/cbf.3722] [PMID: 35707967]
[5]
Rehman, S.; Mohammad, A.; Zeeshan, R. Effect of non-enzymatic glycosylation in the epigenetics of cancer. Semin. Cancer Biol., 2020, 83, 543-555.
[http://dx.doi.org/10.1016/j.semcancer.2020.11.019] [PMID: 33276090]
[6]
Ahmad, S.; Khan, H.; Siddiqui, Z.; Khan, M.Y.; Rehman, S.; Shahab, U.; Godovikova, T.; Silnikov, V.; Moinuddin AGEs, RAGEs and s-RAGE; friend or foe for cancer. Semin. Cancer Biol., 2018, 49, 44-55.
[http://dx.doi.org/10.1016/j.semcancer.2017.07.001] [PMID: 28712719]
[7]
Ji, X.; Ge, L.; Liu, C.; Tang, Z.; Xiao, Y.; Chen, W.; Lei, Z.; Gao, W.; Blake, S.; De, D.; Shi, B.; Zeng, X.; Kong, N.; Zhang, X.; Tao, W. Capturing functional two-dimensional nanosheets from sandwich-structure vermiculite for cancer theranostics. Nat. Commun., 2021, 12(1), 1124.
[http://dx.doi.org/10.1038/s41467-021-21436-5] [PMID: 33602928]
[8]
Bartsch, H. DNA adducts in human carcinogenesis: Etiological relevance and structure-activity relationship. Mutat. Res. Rev. Genet. Toxicol., 1996, 340(2-3), 67-79.
[http://dx.doi.org/10.1016/S0165-1110(96)90040-8] [PMID: 8692183]
[9]
Ahmad, S.; Firoz, A.; Uzma, S. Do all roads lead to the Rome? The glycation perspective! Semin. Cancer Biol., 2017, 49, 9-19.
[http://dx.doi.org/10.1016/j.semcancer.2017.10.012] [PMID: 29113952]
[10]
Ahmad, S. Physicochemical characterization of in vitro ldl glycation and its inhibition by ellagic acid (EA): An in vivo approach to inhibit diabetes in experimental animals. Biomed Res Int, 2022, 2022, 5583298.
[http://dx.doi.org/10.1155/2022/5583298] [PMID: 35097119]
[11]
Kong, N.; Zhang, H.; Feng, C. Arsenene-mediated multiple independently targeted reactive oxygen species burst for cancer therapy. Nat. Commun, 2021, 12(1), 1-8.
[http://dx.doi.org/10.1038/s41467-021-24961-5]
[12]
Lobo, V.; Patil, A.; Phatak, A.; Chandra, N. Free radicals, antioxidants and functional foods: Impact on human health. Pharmacogn. Rev., 2010, 4(8), 118-126.
[http://dx.doi.org/10.4103/0973-7847.70902] [PMID: 22228951]
[13]
Ahmad, S.; Khan, H.; Shahab, U.; Rehman, S.; Rafi, Z.; Khan, M.Y.; Ansari, A.; Siddiqui, Z.; Ashraf, J.M.; Abdullah, S.M.; Habib, S.; Uddin, M. Protein oxidation an overview of metabolism of sulphur containing amino acid cysteine. Front. Biosci., 2017, 9(1), 71-87.
[http://dx.doi.org/10.2741/s474] [PMID: 27814576]
[14]
Moinuddin; Dixit, K.; Ahmad, S.; Shahab, U.; Habib, S.; Naim, M.; Alam, K.; Ali, A. Human DNA damage by the synergistic action of 4-aminobiphenyl and nitric oxide: An immunochemical study. Environ. Toxicol., 2014, 29(5), 568-576.
[http://dx.doi.org/10.1002/tox.21782] [PMID: 22610904]
[15]
Khan, M.Y.; Alouffi, S.; Ahmad, S. Immunochemical studies on native and glycated LDL – An approach to uncover the structural perturbations. Int. J. Biol. Macromol., 2018, 115, 287-299.
[http://dx.doi.org/10.1016/j.ijbiomac.2018.04.016] [PMID: 29634967]
[16]
Rehman, S.; Alouffi, S.; Faisal, M.; Qahtan, A.A.; Alatar, A.A.; Ahmad, S. Methylglyoxal mediated glycation leads to neo-epitopes generation in fibrinogen: Role in the induction of adaptive immune response. Int. J. Biol. Macromol., 2021, 175, 535-543.
[http://dx.doi.org/10.1016/j.ijbiomac.2021.01.197] [PMID: 33529635]
[17]
Shahab, U.; Ahmad, S.; Moinuddin; Dixit, K.; Habib, S.; Alam, K.; Ali, A. Hydroxyl radical modification of collagen type II increases its arthritogenicity and immunogenicity. PLoS One, 2012, 7(2), e31199.
[http://dx.doi.org/10.1371/journal.pone.0031199] [PMID: 22319617]
[18]
Ahmad, S.; Moinuddin; Dixit, K.; Shahab, U.; Alam, K.; Ali, A. Genotoxicity and immunogenicity of DNA-advanced glycation end products formed by methylglyoxal and lysine in presence of Cu2+. Biochem. Biophys. Res. Commun., 2011, 407(3), 568-574.
[http://dx.doi.org/10.1016/j.bbrc.2011.03.064] [PMID: 21420380]
[19]
Shahab, U.; Moinuddin; Ahmad, S.; Dixit, K.; Abidi, S.M.A.; Alam, K.; Ali, A. Acquired immunogenicity of human DNA damaged by N-hydroxy-N-acetyl-4-aminobiphenyl. IUBMB Life, 2012, 64(4), 340-345.
[http://dx.doi.org/10.1002/iub.1008] [PMID: 22378795]
[20]
Siddiqui, Z.; Ishtikhar, M.; Moinuddin; Ahmad, S. d-Ribose induced glycoxidative insult to hemoglobin protein: An approach to spot its structural perturbations. Int. J. Biol. Macromol., 2018, 112, 134-147.
[http://dx.doi.org/10.1016/j.ijbiomac.2018.01.161] [PMID: 29378270]
[21]
Mustafa, I.; Ahmad, S.; Dixit, K.; Moinuddin; Ahmad, J.; Ali, A. Glycated human DNA is a preferred antigen for anti-DNA antibodies in diabetic patients. Diabetes Res. Clin. Pract., 2012, 95(1), 98-104.
[http://dx.doi.org/10.1016/j.diabres.2011.09.018] [PMID: 22001283]
[22]
Shahab, U.; Moinuddin; Ahmad, S.; Dixit, K.; Habib, S.; Alam, K.; Ali, A. Genotoxic effect of N-hydroxy-4-acetylaminobiphenyl on human DNA: implications in bladder cancer. PLoS One, 2013, 8(1), e53205.
[http://dx.doi.org/10.1371/journal.pone.0053205] [PMID: 23382838]
[23]
Ahmad, S.; Moinuddin; Shahab, U.; Habib, S.; Salman Khan, M.; Alam, K.; Ali, A. Glycoxidative damage to human DNA: Neo-antigenic epitopes on DNA molecule could be a possible reason for autoimmune response in type 1 diabetes. Glycobiology, 2014, 24(3), 281-291.
[http://dx.doi.org/10.1093/glycob/cwt109] [PMID: 24347633]
[24]
Ashraf, J.M.; Ahmad, S.; Rabbani, G.; Hasan, Q.; Jan, A.T.; Lee, E.J.; Khan, R.H.; Alam, K.; Choi, I. 3-Deoxyglucosone: A potential glycating agent accountable for structural alteration in H3 histone protein through generation of different AGEs. PLoS One, 2015, 10(2), e0116804.
[http://dx.doi.org/10.1371/journal.pone.0116804] [PMID: 25689368]
[25]
Faisal, M.; Shahab, U.; Alatar, A.A.; Ahmad, S. Preferential recognition of auto-antibodies against 4- hydroxynonenal modified DNA in the cancer patients. J. Clin. Lab. Anal., 2017, 31(6), e22130.
[http://dx.doi.org/10.1002/jcla.22130] [PMID: 28105689]
[26]
Akhter, F.; Khan, M.S.; Singh, S.; Ahmad, S. An immunohistochemical analysis to validate the rationale behind the enhanced immunogenicity of D-ribosylated low density lipo-protein. PLoS One, 2014, 9(11), e113144.
[http://dx.doi.org/10.1371/journal.pone.0113144] [PMID: 25393017]

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy