Involvements of mitochondrial thioredoxin reductase (TrxR2) in cell proliferation.
Mammalian cells contain two forms of thioredoxin reductase (TrxR), cytosolic TrxR1 and mitochondrial TrxR2. To investigate the biological roles of TrxR2, we generated stable HeLa cell lines expressing a dominant negative form of TrxR2 (TrxR2DN) under the control of the tetracycline-off system. We observed that TrxR2DN-induced cells, following stimulation with EGF, produced more hydrogen peroxide than uninduced cells. The extent of protein tyrosine phosphorylation of many proteins including ERK was higher in TrxR2DN-induced cells than in uninduced cells when stimulated with fetal bovine serum or EGF. Induction of TrxR2DN also resulted in the increased rate of progression of G1 to S phase in cell cycle and cell proliferation and affected the expression of many proteins involved in cell cycle. These results suggest that TrxR2 participates in the regulation of protein tyrosine phosphorylation and cell growth as a component of the mitochondria specific H2O2-eliminating system that includes peroxiredoxin III and thioredoxin 2.
Kim
Mi-Ra
MR
Department of Biochemistry and Molecular Biology, College of Medicine, Yeungnam University, 317-1 Daemyong-Dong, 705-717, Daegu, Republic of Korea.
Chang
Ho-Sung
HS
Kim
Byung-Hak
BH
Kim
Seongyong
S
Baek
Suk-Hwan
SH
Kim
Jung Hye
JH
Lee
Seung-Rock
SR
Kim
Jae-Ryong
JR
D002453:Cell Cycle; D002455:Cell Division; D004815:Epidermal Growth Factor / Q000494:pharmacology; D005786:Gene Expression Regulation; D006367:HeLa Cells; D006801:Humans; D006861:Hydrogen Peroxide / Q000032:analysis; D008928:Mitochondria / Q000201:enzymology*; D009154:Mutation; D010750:Phosphoproteins / Q000737:chemistry / Q000378:metabolism; D010766:Phosphorylation; D013752:Tetracycline / Q000494:pharmacology; D054482:Thioredoxin Reductase 2; D013880:Thioredoxin-Disulfide Reductase / Q000235:genetics / Q000502:physiology*; D014443:Tyrosine / Q000378:metabolism
D010750:Phosphoproteins; D014443:Tyrosine; D004815:Epidermal Growth Factor; D006861:Hydrogen Peroxide; C516127:TXNRD2 protein, human; D054482:Thioredoxin Reductase 2; D013880:Thioredoxin-Disulfide Reductase; D013752:Tetracycline