Thioredoxin peroxidase is a novel inhibitor of apoptosis with a mechanism distinct from that of Bcl-2.
Thioredoxin peroxidase (TPx) is a member of a newly discovered family of proteins that are conserved from yeast to mammals and to which natural killer enhancing factor belongs. These proteins are antioxidants that function as peroxidases only when coupled to a sulfhydryl reducing system. The physiological function of TPx in cells is not yet known. Here we demonstrate that when the human TPx II, a member of this family, is stably overexpressed in Molt-4 leukemia cells, it protects from apoptosis induced by serum deprivation, ceramide, or etoposide. TPx II, like Bcl-2, is able to inhibit release of cytochrome c from mitochondria to cytosol, and it inhibits lipid peroxidation in cells. TPx II, unlike Bcl-2, could prevent hydrogen peroxide accumulation in cells, suggesting that it functions upstream of Bcl-2 in the protection from apoptosis and may be implicated as an endogenous regulator of apoptosis.
Zhang
P
P
Department of Medicine, Duke University Medical Center, Durham, North Carolina 27710, USA.
Liu
B
B
Kang
S W
SW
Seo
M S
MS
Rhee
S G
SG
Obeid
L M
LM
D000975:Antioxidants / Q000378:metabolism*; D017209:Apoptosis; D002374:Catalase / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000378:metabolism*; D006801:Humans; D008054:Lipid Peroxides / Q000378:metabolism; D009363:Neoplasm Proteins; D010544:Peroxidases / Q000378:metabolism*; D061105:Peroxiredoxin III; D054464:Peroxiredoxins; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D011506:Proteins / Q000378:metabolism*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism*; D013482:Superoxide Dismutase / Q000378:metabolism; D014407:Tumor Cells, Cultured
D000975:Antioxidants; D004791:Enzyme Inhibitors; D008054:Lipid Peroxides; D009363:Neoplasm Proteins; D011506:Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D010544:Peroxidases; C516115:PRDX3 protein, human; D061105:Peroxiredoxin III; D054464:Peroxiredoxins; D002374:Catalase; D013482:Superoxide Dismutase; D011065:Poly(ADP-ribose) Polymerases