Biomedical Engineering Reference
In-Depth Information
FIGURE 7.19 NADPH oxidase-mediated ROS formation. Abbreviations:
NADPH, nicotinamide adenine dinucleotide phosphate; NOX, NADPHoxidase;
FAD, flavin adenine dinucleotide; MPO, myeloperoxidase; DUOX, dual oxi-
dase; R, extracellular substrates. Source: Modified from Lambeth (2004).
has greater diffusibility than superoxide or hydroxyl radicals, allowing
it to selectively oxidize sulfhydryl groups of specific cysteine residues
on proteins resulting in several reversible modifications including the
formation of protein-protein (Pr-Pr) and GS-protein disulfides (GS-Pr,
mixed disulfides) (Thannickal and Fanburg, 2000; Janssen-Heininger et
al., 2008). At physiologically relevant concentrations of hydrogen
peroxide, these modifications are reversible and constitute a control
mechanism of protein function, whereas higher exposures could lead to
excessive and irreversible S-oxidation resulting in loss of protein
function and pathological consequences. Major cellular sources of
ROS include the mitochondrial electron transport chain, LPOs, as
well as NOXs (Lander, 1997). NOX enzymes are commonly known
for their role in phagocytes for initiating the “respiratory burst” by
producing high concentrations of superoxide and hydrogen peroxide.
Homologs were later found to be expressed ubiquitously in nonpha-
gocytic cells, although they produce more physiological levels of ROS
involved in signal transduction (Lambeth, 2004; Brown and Griendling,
