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Salivary antigen‐5/CAP family members are Cu 2+ ‐dependent antioxidant enzymes which negatively modulate platelet function
Author(s) -
Assumpcao Teresa,
Ma Dongying,
Schwarz Alexandra,
Reiter Karine,
Santana Jaime M.,
Andersen John F.,
Ribeiro Jose M. C.,
Nardone Glenn,
Yu Lee L.,
Francischetti Ivo M. B.
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.lb173
Subject(s) - xanthine oxidase , chemistry , superoxide dismutase , antioxidant , biochemistry , enzyme , antigen , microbiology and biotechnology , biology , immunology
The function of the antigen‐5/CAP family of salivary gland (SG) proteins ubiquitously found in bloodsucking animals has remained elusive for decades. Antigen 5 members from the hematophagous bugs Dipetalogaster maxima (DMAV) and Triatoma infestans (TIAV) were expressed and discovered to attenuate platelet aggregation by low doses of collagen (<1 μg/mL) but no other agonists. This inhibitory profile resembles the effects of antioxidants (e.g., superoxide dismutase [SOD]) in platelet function. Accordingly, our results demonstrate that DMAV blunts the luminescence signal of O 2 − generated by phorbol myristate acetate (PMA)‐stimulated neutrophils. Moreover, Cu 2+ ‐DMAV was found to inhibit cytochrome c reduction by O 2 − generated by the xanthine/xanthine oxidase implying that it exhibits antioxidant activity. Mechanistically, ICP‐MS and fluorescence spectroscopy revealed that DMAV, like SOD, interacts with Cu 2+ which provides redox potential for catalytic removal of O 2 − . Notably, SG of D. maxima with native DMAV contain Cu 2+ and display metal‐dependent antioxidant properties. Antigen‐5/CAP emerges as a novel family of Cu 2+ ‐dependent antioxidant enzymes that negatively modulate platelet aggregation by a unique salivary mechanism.