Cytochromes, reactive oxygen species and responses of the oxygen sensing signal pathway
Respiratory Research volume 2, Article number: 5.4 (2001)
The heterogeneous oxygen partial pressure (PO2) distribution in mammalian organs requires for triggering gene expression and ion channel conductivity an O2-sensing signal cascade with three responses: optimizing of cellular functions during normoxia, adaptation of cell function under hypoxia and survival of cell function to withstand anoxia. It is not known whether these different responses are induced by various O2 sensing signal cascades. One signal casade, however, is supposed to consist of mitochondrial and/or non-mitochondrial heme proteins sensing oxygen with subsequent second messenger formation such as reactive oxygen species (ROS), in particular hydroxyl radicals (OH) which influence transcription factor stability as well as ion channel pore formation. NADPH oxidase isoforms with different gp91phox subunits as well as an unusual cytochrome c oxidase (CYT) with a hemea/hemea3 relationship of 9:91 as detected by light absorption photometry in the carotid body as well as human liver tumor cells (HepG2) will be discussed as putative oxygen sensor proteins. Whereas CYT might be of special importance for the carotid body, NADPH isoforms generating ROS in dependence on PO2 are considered as more general cellular O2 sensors. The formation of OH by a perinuclear Fenton reaction from hydrogen peroxide (H2O2) is imaged three dimensionally by 1 and 2 photon confocal laser microscopy in HepG2 cells using dihydrorhodamine 123 or 2'7' dichlorodihydrofluorescin as indicators. Hot spots of OH generation are seen predominantly in the endoplasmatic reticulum (ER) but also in mitochondria (MIT). It is concluded, that heme and non-heme iron binding proteins in the ER and MIT compartment represent the perinuclear hot spots which degrade H2O2 originating from NADPH oxidase isoforms.
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Acker, H. Cytochromes, reactive oxygen species and responses of the oxygen sensing signal pathway. Respir Res 2 (Suppl 1), 5.4 (2001). https://doi.org/10.1186/rr117