Mechanisms involved in the protective effect of estradiol-17beta on lipid peroxidation and DNA damage.
Previous studies from our laboratory have shown that estrogens can protect against lipoprotein peroxidation and DNA damage. In this study, the mechanism of estradiol-17beta (E2) action was investigated by comparing E2 with selective scavengers of reactive oxygen species (ROS) in terms of inhibition of 1) human low-density lipoprotein (LDL) peroxidation (measured by the diene conjugation method) and 2) DNA damage (measured by the formation of strand breaks in supercoiled OX-174 RFI DNA). In addition, the direct effect of E2 on the generation of individual ROS was also measured. By use of ROS scavengers, it was determined that lipoprotein peroxidation was predominantly due to superoxide (39%), with some contributions from hydrogen peroxide (23%) and peroxy (38%) radicals. E2 was a more effective inhibitor of peroxidation than all the ROS scavengers combined. In DNA damage, scavengers of hydrogen peroxide, hydroxyl, and superoxide radical offered significant protection (49-65%). E2 alone offered a similar degree of protection, and no additional effect was evident when it was combined with ROS scavengers. E2 caused a significant reduction (37%) in the production of superoxide radical by bovine heart endothelial cells in culture but had no effect on the formation of either hydrogen peroxide or hydroxyl radicals. These studies show that 1) the protection offered by E2 in terms of lipid peroxidation could be due to its ability to inhibit generation of superoxide radical and prevent further chain propagation, and 2) in DNA damage protection, E2 mainly appears to inhibit chain propagation.
Ayres
S
S
Interdisciplinary Graduate Studies Program, Department of Internal Medicine, University of Cincinnati Medical Center, Cincinnati, Ohio 45267-0540, USA.
Abplanalp
W
W
Liu
J H
JH
Subbiah
M T
MT
D000818:Animals; D002417:Cattle; D004249:DNA Damage; D004958:Estradiol / Q000494:pharmacology*; D005260:Female; D016166:Free Radical Scavengers; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism; D017665:Hydroxyl Radical / Q000378:metabolism; D015227:Lipid Peroxidation; D008077:Lipoproteins, LDL / Q000097:blood; D008297:Male; D009206:Myocardium / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D013481:Superoxides / Q000378:metabolism
D016166:Free Radical Scavengers; D008077:Lipoproteins, LDL; D017382:Reactive Oxygen Species; D013481:Superoxides; D017665:Hydroxyl Radical; D004958:Estradiol; D006861:Hydrogen Peroxide