A striking common O‐linked N‐acetylglucosaminyl moiety between cruzipain and myosin

Abstract

Single units of O-linked N-acetylglucosamine (GlcNAc), usually components of nuclear and cytoplasmatic proteins, are present at the C-terminal domain of cruzipain (Cz), a lysosomal major antigen from Trypanosoma cruzi. On the other hand, antibodies directed against some self-antigens like myosin are associated with Chagas heart disease. The participation of O-GlcNAc moieties in the molecular antigenicity of Cz was determined using GlcNAc linked to aprotinin by ELISA. The immune cross-reactivity between Cz and myosin is mainly focused in the C-T domain. ELISA inhibition assays using rabbit sera specific for Cz and C-T in conjunction with immune-gold electron microscopy analysis of heart tissues from mice immunized with C-T confronted with polyclonal rabbit sera specific for Cz and C-T prior and after myosin adsorption provided evidence which indicates that O-GlcNAc moieties constitute a common epitope between Cz and either myosin or other cardiac O-GlcNAc-containing proteins, showing a new insight into the molecular immune pathogenesis of Chagas heart disease.

Involvement of sulfates from cruzipain, a major antigen of Trypanosoma cruzi, in the interaction with immunomodulatory molecule Siglec-E

“…Our results in conjunction with those reported in Dyctiostelium discoydeum are, as far as we know, the only ones describing the antigenic properties of this type of structures [20,58]. On the other hand, sera from chronically T. cruziinfected subjects with mild disease displayed higher levels of IgG2 antibodies specific for sulfated epitopes compared with those in more severe forms of the disease, suggesting a potential role for sulfate moieties in the control of chronic T. cruzi infection [20,31]. Recently, we found that synthetic anionic sugar conjugates containing GlcNAc6S competitively inhibit the binding of affinity-purified rabbit anti-C-T IgG to the C-terminal extension of Cz.…”

“…Rabbits (New Zealand white lineage) were immunized with Cz and C-T prior to and after desulfation, extracted from polyacrylamide gels (three doses of 50 µg protein intradermal via, in each case), as described [31]. Experimental procedures were conducted in the INP, "Dr Mario Fatala Chaben," Ministerio de Salud, Argentina, in accordance with the ethical legislations and regulatory entities, established in Argentina and International Guides for care and use of laboratory animals.…”

Association of L-Ficolin Levels and FCN2 Genotypes with Chronic Chagas Disease

“…It was not associated with respiratory tract infections in Dutch children [35], nor with invasive pneumococcal disease [36], rheumatoid arthritis [37] and Behçet’s disease in Japan [38]. Interestingly, FCN2*258S, also known as FCN2-C , has increased N-acetyl-D-glucosamine (GlcNAc) binding capacity [11] and O -linked GlcNAc moieties constitute a common epitope between cruzipain, a major T. cruzi antigen, and either myosin or other cardiac O-GlcNAc-containing proteins [39]. Higher GlcNAc binding capacity of this variant may thus correlate with complement activation and destructive deposition of membrane attack complexes (MAC) on muscle tissues of patients with cardiodigestive manifestations.…”

Three Decades of Research on O-GlcNAcylation – A Major Nutrient Sensor That Regulates Signaling, Transcription and Cellular Metabolism

“…O-GlcNAcylation also regulates growth hormone signaling in plants ( 27 ), protects cells from acute stresses ( 47 ), and modulates transition through the cell cycle ( 48 ). Even though O-GlcNAcylation has not yet been documented to occur in yeast, such as Saccharomyces cerevisiae or Schizosaccharomyces pombe , O -GlcNAc does occur in some of oldest known eukaryotes ( 49 ), including in some important human parasites ( 50 – 52 ). In certain bacteria, O-GlcNAcylation regulates flagellar motility ( 53 ), and in Streptococcus pneumonia , O-GlcNAcylation of an adhesion plays a role in infection and pathogenesis ( 54 ).…”