The
superoxide generating
enzyme NADPH oxidase has received much attention as a major cause of oxidative stress underlying
vascular disease. However, there is increasing evidence that
oxidant signaling involving
NADPH oxidase has other important roles in cell biology. Nox family
proteins are the catalytic, electron-transporting subunits of the
NADPH oxidase enzyme complex. It is now clear that
reactive oxygen species (ROS) generated by
NADPH oxidase participate in intracellular signaling processes that regulate cell differentiation and proliferation. These mechanisms are important in tissue repair and
tumorigenesis, diverse conditions where cell proliferation is required, but when poorly controlled the generation of ROS is obviously detrimental. Indeed,
NADPH oxidase-mediated cell proliferation has been observed in a wide range of cell types including those found in blood vessels, kidney, liver, skeletal muscle precursors, neonatal cardiac myocytes, lung epithelial cells, gastric mucosa, brain microglia, and a variety of
cancer cells.
NADPH oxidases act not as isolated elements downstream of a particular pathway, but rather may amplify multiple
receptor tyrosine kinase-mediated processes by inhibiting
protein tyrosine phosphatases. Therefore,
NADPH oxidase-mediated redox signaling may represent a unique intracellular amplifier of diverse signaling pathways involved in tissue repair processes such as cell proliferation, wound healing, angiogenesis and
fibrosis. Recent studies also suggest that
NADPH oxidase is involved in differentiation of stem cells. As occurs in unresolved
inflammation, however, hyperactivity of this
enzyme system leads to tissue injury. Thus modulating
NADPH oxidase may have significant impacts on regenerative medicine and tissue engineering, such as growing heart muscle.