Preferential recognition of peroxynitrite modified human DNA by circulating autoantibodies in cancer patients

Habib, Safia; Moinuddin, Mohammed; Ali, Asif; Ali, Rashid

doi:10.1016/j.cellimm.2008.08.002

Cited by 30 publications

(18 citation statements)

References 23 publications

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“…Increased absorbance in 300-400 nm range [31] and its usefulness in glycation of DNA/nucleotide/proteins with reducing sugars has been well documented [37,38]. The systemic decrease in T m values of modified-DNA samples could be attributed to strand breaks, unstaking and base modification that may lead to altered hydrogen bonding between base pairs [35,36]. Strand breaks were specifically confirmed from positive nuclease S1 action on glucose-modified samples compared to native DNA, which remained resistant to nuclease S1.…”

Section: Discussionmentioning

confidence: 98%

“…7a). Reaction of glycation induced intermediates and/or superoxide radicals with sugar-phosphate back bone of DNA might be responsible behind generation of strand breaks/small size DNA fragments showing faster mobility [34][35][36]. In order to confirm the generation of single strand breaks, samples were digested with nuclease S1 (20 U/mg DNA) for 30 min and electrophoresed on 0.8% agarose gel.…”

Section: Agarose Gel Electrophoresismentioning

confidence: 99%

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Physicochemical analysis of structural changes in DNA modified with glucose

Ashraf

Arif

Dixit

et al. 2012

International Journal of Biological Macromolecules

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Section: Discussionmentioning

confidence: 98%

Section: Agarose Gel Electrophoresismentioning

confidence: 99%

Physicochemical analysis of structural changes in DNA modified with glucose

Ashraf

Arif

Dixit

et al. 2012

International Journal of Biological Macromolecules

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“…2). The damaged DNA has been reported to be highly immunogenic, implicating its role in the production of antibodies in diseases like SLE and Cancer [42][43][44].…”

Section: Indirect Effect Of Nomentioning

confidence: 99%

Biochemistry of Nitric Oxide

2011

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Nitric oxide (NO) a free radical having both cytoprotective as well as tumor promoting agent is formed from L-arginine by converting it to L-citrulline via nitric oxide synthase enzymes. The reaction product of nitric oxide with superoxide generates potent oxidizing agent, peroxynitrite which is the main mediator of tissue and cellular injury. Peroxynitrite is reactive towards many biomolecules which includes amino acids, nucleic acid bases; metal containing compounds, etc. NO metabolites may play a key role in mediating many of the genotoxic/ carcinogenic effects as DNA damage, protein or lipid modification, etc. The basic reactions of nitric oxide can be divided as direct effect of the radical where it alone plays a role in either damaging or protecting the cell milieu and an indirect effect in which the byproducts of nitric oxide formed by convergence of two independent radical generating pathways play the role in biological reactions which mainly involve oxidative and nitrosative stress. Nitric oxide is also capable of directly interacting with mitochondria through inhibition of respiration or by permeability transition. Reaction of nitric oxide with metal ions include its direct interaction with the metals or with oxo complexes thereby reducing them to lower valent state. Excessive production of nitric oxide can be studied by inhibiting the synthetic pathway of nitric oxide using both selective or specific nitric oxide synthase inhibitor or nonselective nitric oxide synthase inhibitor with respect to isoforms of nitric oxide.Keywords Nitric oxide Á Nitric oxide synthase Á Nitric oxide inhibitors Á Generation of nitric oxide Á Cancer Á Systemic lupus erythematosus Á Direct and indirect effect of nitric oxide Á Effect of nitric oxide on mitochondria

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“…ELISA was performed on polystyrene plates with slight modifications [29]. Briefly, 96 wells microtitre plates were coated with 100 μl of native and glucose-modified HSA (10 μg/mL in protein coating buffer) and incubated for 2 hrs at 37°C followed by overnight incubation at 4°C.…”

Section: Methodsmentioning

confidence: 99%

Nonenzymatic glycosylation of human serum albumin and its effect on antibodies profile in patients with diabetes mellitus

2017

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BackgroundAlbumin glycation and subsequent formation of advanced glycation end products (AGEs) correlate with diabetes and associated complications.MethodsHuman Serum Albumin (HSA) was modified with D-glucose for a 40 day period under sterile conditions at 37°C. Modified samples along with native HSA (unmodified) were analyzed for structural modifications by UV and fluorescence, FTIR, Liquid chromatography mass spectrometry (LCMS) and X–ray crystallography. New-Zealand white female rabbits immunized with AGEs, represent auto-antibodies formation as assessed by competitive and direct binding enzyme-linked immunosorbent assay (ELISA). Neo-epitopesagainst In-vitro formed AGEs were characterized in patients with diabetes mellitus type 2 (n = 50), type 1 (n = 50), gestational diabetes (n = 50) and type 2 with chronic kidney disease (CKD) with eGFR level 60–89 mL/min (n = 50) from serum direct binding ELISA.ResultsGlycated-HSA showed amarked increase in hyperchromicity of 65.82%,71.98%, 73.62% and 76.63% at λ280 nm along with anincreasein fluorescence intensity of 65.82%, 71.98%, 73.62% and 76.63% in glycated-HSA compared to native. FTIR results showed theshifting of Amide I peak from 1656 cm_1 to 1659 cm_1 and Amide II peak from 1554 cm_1 to 1564 cm_1 in glycated-HSA, with anew peak appearance of carbonyl group at 1737 cm-1. LCMS chromatogram of glycated-HSA showed thepresence of carboxymethyl lysine (CML) at 279.1 m/z. Immunological analysis showed high antibody titre>1:12,800 in theserum of rabbits immunized with glycated-HSA (modified with 400 mg/dL glucose) and inhibition of 84.65% at anantigen concentration of 20μg/mL. Maximum serum auto-antibody titre was found in T2DM (0.517±0.086), T1DM (0.108±0.092), GDM (0.611±0.041) and T2DM+CKD (0.096±0.25) patients immunized with glycated-HSA (modified with 400 mg/dL glucose).ConclusionsNon-enzymatic glycosylation of HSA manifests immunological complications in diabetes mellitus due to change in its structure that enhances neo-epitopes generation.

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Preferential recognition of peroxynitrite modified human DNA by circulating autoantibodies in cancer patients

Cited by 30 publications

References 23 publications

Physicochemical analysis of structural changes in DNA modified with glucose

Physicochemical analysis of structural changes in DNA modified with glucose

Biochemistry of Nitric Oxide

Nonenzymatic glycosylation of human serum albumin and its effect on antibodies profile in patients with diabetes mellitus

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