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Science Forum Index » Life Extension Forum » D3, thioredoxin, and immune function.
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| Tim |
 Posted: Fri Jan 09, 2004 1:11 pm |
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Med Klin (Munich). 1999 Oct 15;94 Suppl 3:29-34. Related Articles,
Links
[Expression of selenoproteins in monocytes and
macrophages--implications for the immune system]
[Article in German]
Ebert-Dumig R, Seufert J, Schneider D, Kohrle J, Schutze N, Jakob F.
Interdisziplinares Zentrum fur Klinische Forschung, Universitat
Wurzburg.
Monocytes differentiate from myeloid precursors towards the macrophage
state of differentiation under the influence of 1,25-dihydroxy
vitamins D3 (1,25 [OH]2 vitamin D3) and other factors and this is
further propagated by colony stimulating factors (MCSF and GMCSF).
Macrophage activation and phagocytosis of foreign particles are
regularly accompanied by a so called "respiratory burst", an increase
in the production of reactive oxygen species (ROS), exerted by the
enzyme complex NADPH oxidase. A number of antioxidant enzymes is
expressed at the same time to protect the cells from the cytotoxic
effects of ROS directed against engulfed microorganisms. The
selenium-dependent glutathione peroxidases and thioredoxin reductases
are important examples. The cytosolic GPx isoenzyme (cGPx) and
thioredoxin reductase alpha (TrxR alpha) are upregulated during the
process of differentiation and under the influence of 1.25 (OH)2
vitamin D3. GPx isoenzymes neutralize H2O2. TrxR reduce
sulfhydryl-groups like in cysteins either directly or via their
cofactor thioredoxin and thus are involved in protein folding and
critical protein-protein and protein-DNA interactions, e.g. modulation
of dimerization and/or DNA-binding and ligand binding of transcription
factors (glucocorticoid receptor and other steroid receptors, NF kappa
B). In addition, the antibiotic peptide NK-lysin was shown to be a
substrate for TrxR alpha, suggesting that TrxR protects the cell
itself from the cytotoxic effects of NK-lysin. Selenium is
incorporated into selenocysteine (Secys) in a regulated fashion in the
presence of a hairpin structure (Secis element) in the 3'UTR of
selenoprotein genes. Secis elements direct the insertion of Secys at
UGA codons, which function as opal stop codons in the absence of a
suitable Secis element and in selenium deficiency. The above mentioned
processes might therefore be altered in relative selenium deficiency
or vice versa be upregulated through selenium supplementation. We have
shown that TrxR alpha is a 1.25 (OH)2 vitamin D3-responsive early gene
in monocytic cells and that TrxR activity as well as GPx activity in
these cells can be upregulated by the addition of selenium in vitro
and ex vivo. Recent work demonstrates that thioredoxin rapidly enters
the cell nucleus upon treatment of cells with H2O2, but little is
known about the compartimentalization of the respiratory burst and the
intracellular localization of antioxidant enzymes during that process.
Macrophage function is insufficient if the generation of a respiratory
burst is altered like in hereditary chronic granulomatous disease on
one hand, but on the other hand is as well disturbed, if there is a
lack in antioxidant enzyme activity. Thioredoxin has been identified
as a lymphocyte growth factor and might therefore be involved in the
crosstalk between macrophages and lymphocytes. The relevance of the
above mentioned and other yet undefined monocytic selenoproteins
remains to be elucidated in detail as well as the relevance of
selenium supplementation in nutrition in general and in situations of
critical infectious disease and autoimmunity.
Publication Types:
Review
Review, Tutorial
PMID: 10554525 [PubMed - indexed for MEDLINE]
Tim |
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