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

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.