DNA microarray reveals increased expression of thioredoxin peroxidase in thioredoxin-1 transfected cells and its functional consequences.
The mammalian thioredoxins are a family of small redox proteins that undergo NADPH dependent reduction by thioredoxin reductase. Reduced thioredoxins reduce oxidized cysteine groups on proteins including transcription factors to increase their binding to DNA, and is a source of reducing equivalents for enzymes such as thioredoxin peroxidase which removes H2O2 and alkyl peroxides. Thioredoxin-1 is over expressed in many human tumors where it is associated with aggressive tumor growth, inhibited apoptosis and decreased patient survival. Transfection of cells with thioredoxin-1 has been shown to increase cell growth and inhibit apoptosis. We have used DNA micro array to investigate the effects of thioredoxin-1 transfection on the expression of a panel of 520 redox, apoptosis and cell growth related genes in MCF-7 human breast cancer cells. One of the genes whose expression was increased as a result of thioredoxin-1 over expression was thioredoxin peroxidase-2. This increase was confirmed by Northern blotting. Transfection of mouse WEHI7.2 thymoma cells with human thioredoxin peroxidase-2 was found to protect the cells from apoptosis induced by H2O2 but not from apoptosis induced by dexamethasone, doxorubicin or etoposide. Thus, increased thioredoxin peroxidase-2 expression does not explain the widespread antiapoptotic effects of thioredoxin-1.
Husbeck
B
B
Arizona Cancer Center, University of Arizona, Tucson 85724-5024, USA.
Berggren
M I
MI
Powis
G
G
D000818:Animals; D017209:Apoptosis; D015870:Gene Expression; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism; D051379:Mice; D009363:Neoplasm Proteins; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D010544:Peroxidases / Q000235:genetics / Q000502:physiology*; D061105:Peroxiredoxin III; D054464:Peroxiredoxins; D012643:Selenium / Q000378:metabolism; D013879:Thioredoxins / Q000096:biosynthesis* / Q000235:genetics; D014162:Transfection; D014407:Tumor Cells, Cultured
D009363:Neoplasm Proteins; C516116:Prdx3 protein, mouse; D013879:Thioredoxins; D006861:Hydrogen Peroxide; D010544:Peroxidases; C516115:PRDX3 protein, human; D061105:Peroxiredoxin III; D054464:Peroxiredoxins; D012643:Selenium