TY - JOUR
T1 - 17β-Estradiol alters oxidative stress response protein expression and oxidative damage in the uterus
AU - Yuan, Lisi
AU - Dietrich, Alicia K.
AU - Nardulli, Ann M.
N1 - Funding Information:
We are indebted to Ken Korach and Sylvia Hewitt (NIEHS, North Carolina), who provided detailed information about the location of ERα-associated gene regions in the uterus and we thank members of the Nardulli lab for technical assistance and helpful discussions. This work was supported by NIH Grant DK 053884 (to AMN). AKD was supported by a predoctoral fellowship from the NIEHS Reproductive Toxicology Training Grant T32 ES007326.
PY - 2014/1/25
Y1 - 2014/1/25
N2 - The steroid hormone 17β-estradiol (E2) has profound effects on the uterus. However, with the E2-induced increase in uterine cell proliferation and metabolism comes increased production of reactive oxygen species (ROS). We examined the expression of an interactive network of oxidative stress response proteins including thioredoxin (Trx), Cu/Zn superoxide dismutase (SOD1), apurinic endonuclease (Ape1), and protein disulfide isomerase (PDI). We demonstrated that treatment of ovariectomized C57BL/6J female mice with E2 increased the mRNA and protein levels of Trx, but decreased SOD1 and Ape1 mRNA and protein expression. In contrast, E2 treatment increased PDI protein levels but had no effect on PDI transcript levels. Interestingly, E2 treatment also increased two markers of cellular damage, lipid peroxidation and protein carbonylation. Our studies suggest that the decreased expression of SOD1 and Ape1 caused by E2 treatment may in the long term result in disruption of ROS regulation and play a role in endometrial carcinogenesis.
AB - The steroid hormone 17β-estradiol (E2) has profound effects on the uterus. However, with the E2-induced increase in uterine cell proliferation and metabolism comes increased production of reactive oxygen species (ROS). We examined the expression of an interactive network of oxidative stress response proteins including thioredoxin (Trx), Cu/Zn superoxide dismutase (SOD1), apurinic endonuclease (Ape1), and protein disulfide isomerase (PDI). We demonstrated that treatment of ovariectomized C57BL/6J female mice with E2 increased the mRNA and protein levels of Trx, but decreased SOD1 and Ape1 mRNA and protein expression. In contrast, E2 treatment increased PDI protein levels but had no effect on PDI transcript levels. Interestingly, E2 treatment also increased two markers of cellular damage, lipid peroxidation and protein carbonylation. Our studies suggest that the decreased expression of SOD1 and Ape1 caused by E2 treatment may in the long term result in disruption of ROS regulation and play a role in endometrial carcinogenesis.
KW - Apurinic endonuclease
KW - Cu/Zn superoxide dismutase
KW - Estrogen receptor a{script}
KW - Oxidative stress
KW - Protein disulfide isomerase
KW - Thioredoxin
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U2 - 10.1016/j.mce.2013.09.023
DO - 10.1016/j.mce.2013.09.023
M3 - Article
C2 - 24103313
AN - SCOPUS:84886255467
SN - 0303-7207
VL - 382
SP - 218
EP - 226
JO - Molecular and Cellular Endocrinology
JF - Molecular and Cellular Endocrinology
IS - 1
ER -