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Analysis of the binding of bovine and human fibrinogen to ferritin: evidence that fibrinogen is a common ferritin-binding protein in mammals

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Abstract

Both human and horse fibrinogen are heme-binding proteins, and horse fibrinogen also exhibits heme-mediated ferritin binding. This study found that bovine and human fibrinogen are heme-mediated ferritin-binding proteins and demonstrated direct binding of bovine ferritin to protoporphyrin (PPIX) and its derivatives or to Zn ions. Binding of bovine and human fibrinogen to bovine spleen ferritin coated on microtiter plate wells was detected using an anti-human fibrinogen antibody, and this binding was inhibited in a dose-dependent manner by hemin (iron-PPIX) and also inhibited by Zn-PPIX. PPIX showed less of an inhibitory effect on the binding of bovine and human fibrinogen to bovine ferritin. The inhibitory effect of Sn-PPIX was similar to that of PPIX, but with respect to human fibrinogen, PPIX did not inhibit the binding of human fibrinogen to ferritin. Bovine fibrinogen immobilized on CNBr-activated Sepharose 4B beads showed affinity for hemin, Sn-PPIX, Zn-PPIX, and iron-free PPIX in the order Sn-PPIX < iron-free PPIX < hemin < Zn-PPIX. The fibrinogen beads also directly bound to zinc ions. These results suggest that bovine fibrinogen is a heme- and zinc-binding protein and that binding of circulating mammalian fibrinogen to ferritin is heme mediated.

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Authors and Affiliations

  1. Laboratory of Veterinary Biochemistry, School of Veterinary Medicine, Kitasato University, Aomori, 034-8628, Japan

    Akiko Okada, Yasunaga Yoshikawa, Kiyotaka Watanabe & Koichi Orino

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  1. Akiko Okada
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  2. Yasunaga Yoshikawa
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  3. Kiyotaka Watanabe
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  4. Koichi Orino
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Correspondence to Koichi Orino.

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Okada, A., Yoshikawa, Y., Watanabe, K. et al. Analysis of the binding of bovine and human fibrinogen to ferritin: evidence that fibrinogen is a common ferritin-binding protein in mammals. Biometals 28, 679–685 (2015). https://doi.org/10.1007/s10534-015-9853-9

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  • DOI: https://doi.org/10.1007/s10534-015-9853-9

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