17beta-estradiol induces protein thiol/disulfide oxidoreductases and protects cultured bovine aortic endothelial cells from oxidative stress.
OBJECTIVE
To examine whether or not estrogens induced the expression of protein thiol/disulfide oxidoreductases such as protein disulfide isomerase (PDI), thioredoxin (Trx), Trx reductase, and glutaredoxin (Grx) in vascular endothelial cells.


METHODS
The regenerative effects of the protein thiol/disulfide oxidoreductases, PDI, Trx and Grx, on oxidatively damaged proteins were assayed using H2O2-inactivated glyceraldehyde-3-phosphate dehydrogenase (GAPDH) as a reporter enzyme. The induction of protein thiol/disulfide oxidoreductases and the accumulation of protein adducts generated by lipid peroxidation were examined by Western blotting in estrogen-treated bovine aortic endothelial cells (BAECs).


RESULTS
Reduced PDI, Trx and Grx regenerated the H2O2-inactivated GAPDH in vitro. The levels of these protein disulfide oxidoreductases in BAECs were increased by pretreatment with 0.01-10 micromol/l 17beta-estradiol, the largest increase (about fourfold of the control) being found for PDI. Other sex hormones such as progesterone and testosterone did not affect the contents of these oxidoreductases in BAECs. 4-Hydroxy-2-nonenal (HNE)-protein adducts, which are generated by lipid peroxidation, were accumulated in BAECs exposed to paraquat, whereas the pretreatment of BAECs with 17beta-estradiol suppressed their accumulation.


CONCLUSIONS
The estrogen-mediated induction of the protein thiol/disulfide oxidoreductases such as PDI, Trx, Trx reductase and Grx suggested a possible involvement of these oxidoreductases in the antioxidant protection of estrogen observed in the vascular system.
Ejima
K
K
Department of Health Development, University of Occupational and Environmental Health, Kitakyushu 807-8555, Japan.
Nanri
H
H
Araki
M
M
Uchida
K
K
Kashimura
M
M
Ikeda
M
M
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D001011:Aorta; D002417:Cattle; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism; D004958:Estradiol / Q000494:pharmacology*; D054477:Glutaredoxins; D018384:Oxidative Stress; D010088:Oxidoreductases; D011490:Protein Disulfide Reductase (Glutathione) / Q000096:biosynthesis*; D019704:Protein Disulfide-Isomerases / Q000378:metabolism; D011506:Proteins / Q000378:metabolism; D013880:Thioredoxin-Disulfide Reductase / Q000378:metabolism; D013879:Thioredoxins / Q000378:metabolism
D000975:Antioxidants; D054477:Glutaredoxins; D011506:Proteins; D004958:Estradiol; D013879:Thioredoxins; D010088:Oxidoreductases; D013880:Thioredoxin-Disulfide Reductase; D011490:Protein Disulfide Reductase (Glutathione); D019704:Protein Disulfide-Isomerases