Glycoxidation of LDL Generates Cytotoxic Adducts and Elicits Humoral Response in Type 2 Diabetes Mellitus

Glycobiology ◽  
2020 ◽  
Author(s):  
Minhal Abidi ◽  
Abdul Rouf Mir ◽  
Farzana Khan ◽  
Asif Ali ◽  
Moin Uddin
Keyword(s):  
Immune Response ◽  
Tertiary Structure ◽  
Competitive Inhibition ◽  
Tail Length ◽  
Antigenic Determinants ◽  
Binding Studies ◽  
Modified Ldl ◽  
Arginine Residues

Abstract This study elucidates the immunological implications of methylglyoxal (MGO) modified LDL in diabetes type 2 patients (T2DM). Under in-vitro modifications, MGO altered the tertiary structure of LDL. TNBS and phenanthrenequinone assays confirmed lysine and arginine residues as main targets of MGO in LDL. HPLC and LCMS studies confirmed the generation of Nϵ-(carboxymethyl) lysine in the modified protein. Comet assay showing increased tail length of DNA in lymphocytes inferred the cytotoxicity of MGO-LDL. The easy penetration of MGO-LDL into the nucleus is possibly a consequence of its reduced size, post-modification, as observed from the studies on hydrodynamic radii studies in DLS experiments. MGO-LDL was found to be more immunogenic, as compared to native LDL, in immunological studies conducted on experimental rabbits. Our results reflect the presence of neo-antigenic determinants on modified LDL. Competitive inhibition ELISA suggested the presence of neo-epitopes with marked immunogenicity eliciting specific immune response. Binding studies on purified IgG confirmed the enhanced and specific immunogenicity of MGO-LDL. Studies on interaction of MGO-LDL with the circulating auto-antibodies from T2DM patients showed high affinity of serum-antibodies towards MGO-LDL. This study suggests a potent role of glycoxidatively modified LDL in the generation of auto-immune response in T2DM patients.

Su.77. Immune Response to T-independent Antigen Type 2 in vitro

2008 ◽  
Vol 127 ◽  
pp. S149
Author(s):  
Ekaterina Sidorova ◽  
Marina Gavrilova ◽  
Irina Chernyshova
Keyword(s):  
Immune Response

Characterization of Glyoxal Modified LDL: Role in the Generation of Circulating Autoantibodies in Type 2 Diabetes Mellitus and Coronary Artery Disease

2021 ◽  
Vol 22 ◽  
Author(s):  
Md Masum Rizwee ◽  
Minhal Abidi ◽  
Safia Habib ◽  
Abdul Rouf Mir ◽  
Asif Ali ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Cardiovascular Disease ◽  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Antigenic Determinants ◽  
Modified Ldl ◽  
Circulating Antibodies ◽  
Artery Disease

Aims: To investigate role of glyoxal modified LDL in immunopathology of diabetes and cardiovascular disease. Background: Glycoxidation of proteins is widely studied in relation to diabetes and cardiovascular disease. Objective: This study probed the glyoxal mediated modifications in LDL, analyzed the immunogenicity of the glycated LDL and ascertained the presence of circulating antibodies against modified LDL in patients with type 2 diabetes mellitus (T2DM), coronary artery disease (CAD) and patients with both (T2DM+CAD). Methods: Glyoxal mediated modifications in LDL were studied by multiple spectroscopic techniques, high performance liquid chromatography and electron microscopy. Immunization studies were carried in New Zealand rabbits. Presence of antibodies against glyoxal modified LDL in immunized rabbits and human subjects were analyzed by ELISA. Results: Glyoxal altered the structural integrity of LDL and lead to the formation of AGEs. It decreased the alpha helix content of LDL; increased β sheet formation; increased carbonyl content and decreased free lysine and arginine content. Modified LDL showed aggregation, generation of of Nε-(Carboxymethyl) lysine and the formation of amorphous type aggregates. It exhibited high antigenicity and generated specific immune response that shared common antigenic determinants with other glycated proteins. Direct binding data showed the presence of anti- glyoxal modified LDL antibodies in patients with T2DM, CAD and patients with both T2DM and CAD. Further analysis in competitive binding assay revealed specific binding characteristics of auto-antibodies. Sera from patients with T2DM+CAD exhibited highest binding with glyoxal modified LDL. Conclusion: Glyoxal modified LDL has neo-antigenic determinants that cause the generation of circulating antibodies in diabetes and coronary artery disease. The study might have potential relevance in biomarker development.

scholarly journals Preparation of the Branch Bark Ethanol Extract in MulberryMorus alba, Its Antioxidation, and Antihyperglycemic ActivityIn Vivo

2014 ◽  
Vol 2014 ◽  
pp. 1-7 ◽  
Author(s):  
Shu Wang ◽  
Meng Fang ◽  
Yong-Lei Ma ◽  
Yu-Qing Zhang
Keyword(s):  
Competitive Inhibition ◽  
Biological Activities ◽  
Ethanol Extract ◽  
Negative Control ◽  
Postprandial Hyperglycemia ◽  
Intragastric Administration ◽  
Type 2 Diabetic

The biological activities of the branch bark ethanol extract (BBEE) in the mulberryMorus albaL. were investigated. The determination of active component showed that the flavonoids, phenols, and saccharides are the major components of the ethanol extract. The BBEE had a good scavenging activity of the 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical with around 100 μg/mL of IC50value.In vitroassay revealed that the BBEE strongly inhibited bothα-glucosidase and sucrase activities whose IC50values were 8.0 and 0.24 μg/mL, respectively. The kinetic analysis showed that the BBEE as a kind ofα-glucosidase inhibitor characterized a competitive inhibition activity. Furthermore, the carbohydrate tolerance of the normal mice was obviously enhanced at 0.5 h(P<0.05)and 1.0 h(P<0.05)after the BBEE intragastric administration as compared to negative control. At 0.5, 1.0, 1.5, and 2.0 h after the intragastric administration with starch, the postprandial hyperglycemia of the type 2 diabetic mice can be significantly decreased(P<0.01)by supplying various concentrations of the BBEE (10–40 mg/kg body weight). Therefore, the BBEE could effectively inhibit the postprandial hyperglycemia as a novelα-glucosidase activity inhibitor for the diabetic therapy.

PDGF receptors in the rat CNS: during late neurogenesis, PDGF alpha-receptor expression appears to be restricted to glial cells of the oligodendrocyte lineage

Development ◽  
1992 ◽  
Vol 115 (2) ◽  
pp. 535-551 ◽  
Author(s):  
N.P. Pringle ◽  
H.S. Mudhar ◽  
E.J. Collarini ◽  
W.D. Richardson
Keyword(s):  
Glial Cells ◽  
Receptor Expression ◽  
Binding Studies ◽  
Temporal And Spatial Distribution ◽  
Inner Limiting Membrane ◽  
Factor Alpha ◽  
The Brain

Using in situ hybridization, we have visualized cells in the rat central nervous system (CNS) that contain mRNA encoding the platelet-derived growth factor alpha receptor (PDGF-alpha R). After embryonic day 16 (E16), PDGF-alpha R mRNA appears to be expressed by a subset of glial cells, but not by neurons. The temporal and spatial distribution of PDGF-alpha R+ cells, together with 125I-PDGF binding studies on subsets of glial cells in vitro, suggests that PDGF-alpha R may be expressed predominantly, or exclusively, by cells of the oligodendrocyte-type-2 astrocyte (O-2A) lineage. This conclusion is supported by the fact that the numbers of PDGF-alpha R+ cells in developing and adult optic nerves correlate well with independent estimates of the number of O-2A progenitor cells in the nerve at equivalent ages. Small numbers of PDGF-alpha R+ cells are present in the brain at E16, at which time they are found outside the subventricular germinal zones, suggesting that these cells do not express PDGF-alpha R until after, or shortly before they start to migrate away from the subventricular layer towards their final destinations. Reduced numbers of PDGF-alpha R+ cells persist in the adult CNS. PDGF-alpha R is also expressed strongly in the meningeal membranes and choroid plexus, and in the inner limiting membrane of the retina.

scholarly journals The analysis of the monoclonal immune response to influenza virus. II. The antigenicity of the viral hemagglutinin.

1976 ◽  
Vol 144 (4) ◽  
pp. 985-995 ◽  
Author(s):  
W Gerhard
Keyword(s):  
Immune Response ◽  
Influenza Virus ◽  
Monoclonal Antibodies ◽  
Influenza Viruses ◽  
Antigenic Determinants ◽  
Humoral Immune ◽  
Viral Hemagglutinin ◽  
Or Groups ◽  
Virus Strains

The antigenicity of the hemagglutinins (HA) of five influenza viruses of the A0 and A1 subtypes has been analyzed by means of monoclonal antibodies of murine origin produced in vitro. Secondary monoclonal anti-HA(PR8) antibodies were able to differentiate 14 antigenic determinants (or groups of determinants) on the HA of five influenza virus strains of the A0 and A1 subtypes. Taking into account that certain pairs of determinants delineated on heterologous HA may reflect the heterogeneity of the humoral immune response to a single homologous determinant, the presence of at least eight determinants (host cell-derived determinants not included) on the homologous HA of PR8 and probably on the HA of influenza viruses in general is postulated. Three types of HA-determinants of A0 and A1 influenza virus strains could be distinguished: strain-specific, partially shared, and determinant(s) common to all five virus strains tested. Roughly 40, 55, and 5%, respectively, of the secondary anti-PR8 antibodies of BALB/c mice were directed against determinants belonging to either of the three types.

scholarly journals Anti-modified LDL antibodies, LDL-containing immune complexes, and susceptibility of LDL to in vitro oxidation in patients with type 2 diabetes

Diabetes ◽  
2000 ◽  
Vol 49 (6) ◽  
pp. 1033-1041 ◽  
Author(s):  
M. A. Mironova ◽  
R. L. Klein ◽  
G. T. Virella ◽  
M. F. Lopes-Virella
Keyword(s):  
Type 2 Diabetes ◽  
Immune Complexes ◽  
Modified Ldl

Clinical implication of detecting sensitization to iodinated radiocontrast media in the basophil activation test by flow cytometry

2021 ◽  
Vol 66 (12) ◽  
pp. 747-754
Author(s):  
N. V. Bychkova ◽  
P. A. Selivanov ◽  
N. M. Kalinina
Keyword(s):  
Flow Cytometry ◽  
Immune Response ◽  
T Lymphocytes ◽  
Basophil Activation Test ◽  
Basophil Activation ◽  
Activation Test ◽  
Radiocontrast Media ◽  
Type 2 Immune Response

The use of iodinated radiocontrast media is necessary for visualization. A number of patients have adverse effects of various nature and severity when these drugs are administered. Routine allergy tests do not provide adequate diagnosis of reactions to drugs in this group. The aim of this work is to assess the capabilities of the basophil activation test to confirm sensitization to non-ionic iodinated radiocontrast media, as well as to select a safe alternative drug in patients with a burdened history. Basophil activation test by flow cytometry was performed in 184 patients The Nikiforov Russian Centre of Emergency and Radiation Medicine» EMERCOM of Russia and 32 volunteers using ultravist, omnipack, and optiray. The presence of sensitization was assessed based on the basophil activation index, as well as spontaneous and anti-IgE antibody-induced activation of basophils and the population of T-lymphocytes type 2 immune response. The volunteers showed no sensitization to iodinated radiocontrast media. In patients with a medium degree of hypersensitivity reaction in vivo, in vitro sensitization to drugs was detected 4 times more often than in patients with a mild degree (51% versus 13.5%). In patients with systemic reactions to the administration of a known drug, in vitro sensitization was confirmed in 86% of cases, while the frequency of detection of sensitization to drugs did not differ. Spontaneous activation of basophils in patients and type 2 T-lymphocytes were 2 times higher than in volunteers. Patients were more likely to have low (less than 30%) activation of basophils for anti-IgE antibodies. The specificity of the basophil activation test with iodinated radiocontrast media was 100% with a sensitivity of 94.1%. Most patients were able to select a non-sensitizing contrast. Inclusion in the algorithm of spontaneous and anti-IgE antibody-induced activation of basophils and a population of T-lymphocytes type 2 immune response will allow the doctor to carry out a personalized approach to the management of patients with a burdened history.

scholarly journals Immunization of BALB/c Mice with Killed Neospora caninum Tachyzoite Antigen Induces a Type 2 Immune Response and Exacerbates Encephalitis and Neurological Disease

2000 ◽  
Vol 7 (6) ◽  
pp. 893-898 ◽  
Author(s):  
Timothy V. Baszler ◽  
Terry F. McElwain ◽  
Bruce A. Mathison
Keyword(s):  
Immune Response ◽  
Neurological Disease ◽  
Neospora Caninum ◽  
Brain Lesions ◽  
Lymphoid Cells ◽  
Interleukin 4 ◽  
Type 2 Immune Response ◽  
Parasite Challenge

ABSTRACT BALB/c mice were immunized subcutaneously with solubleNeospora caninum tachyzoite antigen (NSO) entrapped in nonionic surfactant vesicles (NISVs) or administered with Freund's complete adjuvant (FCA). Following virulent parasite challenge, groups of mice immunized with NSO and either NISVs or FCA had clinical neurological disease and increased numbers of brain lesions compared to groups of mice inoculated with FCA, NISVs, or phosphate-buffered saline (PBS) alone. Increased numbers of brain lesions were statistically significant only between mice immunized with NISV-NSO and NISV- or PBS-treated mice. Following parasite challenge, brain inflammatory infiltrates in all experimental and control groups of mice were relatively similar and consisted of compact infiltrates of macrophages admixed with various numbers of lymphoid cells. Increased brain lesions in NSO-immunized mice were associated with increased antigen-specific interleukin 4 (IL-4) secretion and increased IL-4:gamma interferon secretion ratios from splenocytes in vitro and increased antigen-specific immunoglobulin G1 (IgG1):IgG2a ratios in vivo. Thus, immunization with whole killed N. caninum antigen and either liposoidal or Freund's adjuvant induced a type 2 immune response that was associated with worsened disease. The present studies emphasize the need to identify specific N. caninum antigens or other delivery systems that will elicit protective immune responses to neosporosis.

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