Lung injury and oxidoreductases.
Acute lung injury represents a wide spectrum of pathologic processes, the most severe end of the spectrum being the acute respiratory distress syndrome. Reactive oxygen intermediates have been implicated as important in the pathobiochemistry of acute lung injury. The endogenous sources that contribute to the generation of reactive oxygen intermediates in acute lung injury are poorly defined but probably include the molybdenum hydroxylases, NAD(P)H oxidoreductases, the mitochondrial electron transport chain, and arachidonic acid-metabolizing enzymes. Our laboratory has focused, in particular, on the regulation of two of these enzyme systems, xanthine oxidoreductase (XDH/XO) and NAD(P)H oxidase. We observe that gene expression of XDH/XO is regulatory in a cell-specific manner and is markedly affected by inflammatory cytokines, steroids, and physiologic events such as hypoxia. Posttranslational processing is also important in regulating XDH/XO activity. More recently, the laboratory has characterized an NAD(P)H oxidase in vascular cells. The cytochrome components of the oxidase, gp91 and p22, appear similar to the components present in phagocytic cells that contribute to their respiratory burst. In human vascular endothelial and smooth muscle cells, oncostatin M potently induces gp91 expression. We believe that regulation of gp91 is a central controlling factor in expression of the vascular NAD(P)H oxidase. In summary, the studies support the concept that the oxidoreductases of vascular cells are expressed in a highly regulated and self-specific fashion.
Hoidal
J R
JR
Department of Internal Medicine, University of Utah Health Sciences Center, Salt Lake City 84132, USA. jhoidal@msscc.med.utah.edu
Xu
P
P
Huecksteadt
T
T
Sanders
K A
KA
Pfeffer
K
K
Sturrock
A B
AB
D000818:Animals; D001808:Blood Vessels / Q000201:enzymology; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D008168:Lung / Q000187:drug effects / Q000201:enzymology*; D055370:Lung Injury; D009247:NADH, NADPH Oxidoreductases / Q000235:genetics / Q000378:metabolism; D016877:Oxidants / Q000633:toxicity; D010088:Oxidoreductases / Q000235:genetics / Q000378:metabolism*; D014968:Xanthine Dehydrogenase / Q000235:genetics / Q000378:metabolism; D014969:Xanthine Oxidase / Q000235:genetics / Q000378:metabolism
D016877:Oxidants; D010088:Oxidoreductases; D014968:Xanthine Dehydrogenase; D014969:Xanthine Oxidase; D009247:NADH, NADPH Oxidoreductases