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Multicopper oxidases: an innovative approach for oxygen management of aerobic organisms

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Abstract

Multicopper oxidases (MCOs), such as ascorbic acid oxidase and ceruloplasmin, are multidomain proteins capable of oxidizing many structurally unrelated compounds reducing oxygen to water without ever generating reactive oxygen species. While MCOs show great oxidative versatility, they can only transfer electrons to molecular oxygen, which is the obligate electron acceptor. Therefore, MCOs could also be considered as “O2 consuming enzymes”, thus contributing to create those states of hypoxia that are normally found in tissues, cells and cell compartments. Since hypoxia is also a common feature of many rapidly growing solid tumors, we postulate that the regulation of GPI-ceruloplasmin isoform, present on the surface of the plasma membrane, could be the molecular event in the creation and the maintenance of hypoxia in tumor cells. By silencing the different MCO genes with siRNA, it would appear possible to attempt to overcome tumor hypoxia, thus improving the efficiency of radiotherapy.

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Acknowledgments

We are grateful to Prof. H. J. McArdle for the gift of Fig. 2 [reprinted from Danzeisen R, Ponnambalam S, Lea RG, Page K, Gambling L, McArdle HJ (2000) The effect of ceruloplasmin on iron release from placental (BeWo) cells: evidence for an endogenous Cu oxidase. Placenta 21:805–812. With permission from Elsevier].

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Authors and Affiliations

  1. Department of Pharmaco-Biology, Laboratory of Biochemistry and Molecular Biology, University of Bari, via E. Orabona 4, 70125, Bari, Italy

    Roberto Arrigoni

  2. Consiglio Nazionale delle Ricerche, Institute of Biomembranes and Bioenergetics, University of Bari, via E. Orabona 4, 70125, Bari, Italy

    Roberto Arrigoni

  3. Department of Biology and Plant Pathology, University of Bari, Bari, Italy

    Oreste Arrigoni

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  1. Roberto Arrigoni
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Correspondence to Roberto Arrigoni.

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Arrigoni, R., Arrigoni, O. Multicopper oxidases: an innovative approach for oxygen management of aerobic organisms. Rend. Fis. Acc. Lincei 21, 71–80 (2010). https://doi.org/10.1007/s12210-009-0071-7

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