17 beta-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 pr otein 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 oxidoreduc tases, PDI, Trx and Grx, on oxidatively damaged proteins were assayed using H2O2-inactivated glyceraldehyde-3-phosphate dehydrogenase (GAPDH) as a rep orter enzyme, The induction of protein thiol/disulfide oxidoreductases and the accumulation of protein adducts generated by lipid peroxidation were ex amined by Western blotting in estrogen-treated bovine aortic endothelial ce lls (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 mu mol/l 17 beta-estradiol, the lar gest increase (about fourfold of the control) being found for PDI, Other se x hormones such as progesterone and testosterone did not affect the content s of these oxidoreductases in BAECs. 4-Hydroxy-2-nonenal (HNE)-protein addu cts, which are generated by lipid peroxidation, were accumulated in BAECs e xposed to paraquat, whereas the pretreatment of BAECs with 17 beta-estradio l suppressed their accumulation. Conclusions: The estrogen-mediated induction of the protein thiol/disulfide oxidoreductases such as PDI, Trx, Trx reductase and Grx suggested a possib le involvement of these oxidoreductases in the antioxidant protection of es trogen observed in the vascular system.