Modulation of the thioredoxin system during inflammatory responses and its effect on heme oxygenase-1 expression.
Heme oxygenase (HO) enzymes catalyze the initial reaction in heme catabolism. HO-1 is an inducible isoform that is up-regulated by diverse stimuli, including inflammatory cytokines and factors that promote oxidative stress. HO-1 is a cytoprotective enzyme that degrades heme, a potent oxidant, to generate carbon monoxide, biliverdin (subsequently reduced to bilirubin), and iron. Recently, we found that thioredoxin (TRX), a disulfide reductase enzyme known to be important for the binding of transcription factors to DNA, contributes to the induction of HO-1 by inflammatory mediators. In the present study, we extended this observation and determined that, similar to HO-1, TRX and TRX reductase (TR) are induced by bacterial lipopolysaccharide in macrophages at the level of mRNA and protein. However, maximal induction of TRX and TR precedes that of HO-1. Increased expression of HO-1 in the cytoplasm of inflammatory cells corresponds to a translocation of TRX into the nucleus of these cells. Finally, transfection of TRX into macrophages promoted an increase in HO-1 protein. Taken together, these data support the concept that the TRX system contributes to the up-regulation of HO-1 under conditions associated with increased oxidative stress.
Ejima
Kuniaki
K
Pulmonary and Critical Care, Brigham and Women's Hospital, Boston, MA 02115, USA.
Layne
Matthew D
MD
Carvajal
Irvith M
IM
Nanri
Hiroki
H
Ith
Bonna
B
Yet
Shaw-Fang
SF
Perrella
Mark A
MA
D000818:Animals; D002460:Cell Line; D006321:Heart / Q000187:drug effects; D006419:Heme Oxygenase (Decyclizing) / Q000235:genetics / Q000378:metabolism*; D051547:Heme Oxygenase-1; D007249:Inflammation / Q000378:metabolism*; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008264:Macrophages / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D008565:Membrane Proteins; D051379:Mice; D009206:Myocardium / Q000378:metabolism; D018384:Oxidative Stress; D012333:RNA, Messenger / Q000378:metabolism; D015427:Reperfusion Injury; D013879:Thioredoxins / Q000235:genetics / Q000378:metabolism*
D007527:Isoenzymes; D008070:Lipopolysaccharides; D008565:Membrane Proteins; D012333:RNA, Messenger; D013879:Thioredoxins; D006419:Heme Oxygenase (Decyclizing); D051547:Heme Oxygenase-1; C496542:Hmox1 protein, mouse