Thioredoxin peroxidase-1 (peroxiredoxin-1) is increased in thioredoxin-1 transfected cells and results in enhanced protection against apoptosis caused by hydrogen peroxide but not by other agents including dexamethasone, etoposide, and doxorubicin.
Thioredoxin-1 (Trx-1) is a small redox oncoprotein whose expression is increased in a number of human primary cancers where it is associated with aggressive tumor growth, inhibition of apoptosis and decreased patient survival. We report that Trx-1-transfected MCF-7 human breast cancer cells have increased expression of thioredoxin peroxidase-1 (TrxP-1) a peroxiredoxin family member that scavenges H(2)O(2) using Trx-1 as a source of reducing equivalents. Our work shows that TrxP-1 is more effective than selenium-dependent glutathione peroxidase in protecting cells against H(2)O(2) damage. Transfection of mouse WEHI7.2 lymphoma cells with human TrxP-1 or TrxP-2, but not TrxP-4, protects the cells against H(2)O(2) induced apoptosis but does not protect against apoptosis induced by dexamethasone, etoposide, or doxorubicin. The results show that an increase in TrxP-1 expression contributes to the protection against H(2)O(2) induced apoptosis caused by Trx-1, but does not protect against apoptosis induced by other agents.
Berggren
M I
MI
Arizona Cancer Center, University of Arizona, Tucson, Arizona, 85724-5024, USA.
Husbeck
B
B
Samulitis
B
B
Baker
A F
AF
Gallegos
A
A
Powis
G
G
D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects* / Q000235:genetics / Q000502:physiology*; D001483:Base Sequence; D017931:DNA Primers / Q000235:genetics; D003907:Dexamethasone / Q000494:pharmacology; D004317:Doxorubicin / Q000494:pharmacology; D005047:Etoposide / Q000494:pharmacology; D005260:Female; D015870:Gene Expression; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D051379:Mice; D009363:Neoplasm Proteins; D010544:Peroxidases / Q000235:genetics / Q000378:metabolism*; D061105:Peroxiredoxin III; D054464:Peroxiredoxins; D012643:Selenium / Q000494:pharmacology; D013879:Thioredoxins / Q000235:genetics* / Q000378:metabolism*; D014162:Transfection; D014407:Tumor Cells, Cultured
D000975:Antioxidants; D017931:DNA Primers; D009363:Neoplasm Proteins; C516116:Prdx3 protein, mouse; D013879:Thioredoxins; D005047:Etoposide; D003907:Dexamethasone; D004317:Doxorubicin; D006861:Hydrogen Peroxide; D010544:Peroxidases; C515940:PRDX1 protein, human; C516115:PRDX3 protein, human; D061105:Peroxiredoxin III; D054464:Peroxiredoxins; D012643:Selenium