Estrogen attenuates cell death induced by carboxy-terminal fragment of amyloid precursor protein in PC12 through a receptor-dependent pathway.
In the present study, we investigated effects of estrogen on cell death induced by carboxy-terminal fragment of amyloid precursor protein (CT), a candidate causative substance in the pathogenesis of Alzheimer's disease. 17 beta-Estradiol attenuated CT-induced cell death in PC12 cells, whereas 17 alpha-estradiol, nonestrogenic stereoisomer, did not exert any significant protective effect on CT-induced cell death. These results suggest that protective effects of estrogen may be mediated by estrogen receptor (ER) in PC12 cells. To confirm the results, we determined the effects of tamoxifen, an estrogen receptor antagonist. Tamoxifen blocked the protective effects of 17 beta-estradiol, although it did not affect those of 17 alpha-estradiol. Overall, it might be thought that the protective effect of estradiol on CT-induced cell death is achieved by hormonal properties mediated through the estrogen receptor rather than the structural properties as a reducing agent.
Chae
H S
HS
Department of Anatomy, College of Medicine, Chung-Ang University, Dongjak-ku, Seoul, Korea.
Bach
J H
JH
Lee
M W
MW
Kim
H S
HS
Kim
Y S
YS
Kim
K Y
KY
Choo
K Y
KY
Choi
S H
SH
Park
C H
CH
Lee
S H
SH
Suh
Y H
YH
Kim
S S
SS
Lee
W B
WB
D000544:Alzheimer Disease / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D016564:Amyloid beta-Protein Precursor / Q000378:metabolism*; D000818:Animals; D002245:Carbon Dioxide / Q000037:antagonists & inhibitors / Q000633:toxicity*; D016923:Cell Death / Q000187:drug effects* / Q000502:physiology; D004958:Estradiol / Q000494:pharmacology*; D004965:Estrogen Antagonists / Q000494:pharmacology; D009410:Nerve Degeneration / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D016716:PC12 Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D010446:Peptide Fragments / Q000037:antagonists & inhibitors / Q000633:toxicity*; D017434:Protein Structure, Tertiary / Q000187:drug effects / Q000502:physiology; D051381:Rats; D011960:Receptors, Estrogen / Q000187:drug effects / Q000378:metabolism*; D013629:Tamoxifen / Q000494:pharmacology
D016564:Amyloid beta-Protein Precursor; D004965:Estrogen Antagonists; D018696:Neuroprotective Agents; D010446:Peptide Fragments; D011960:Receptors, Estrogen; D013629:Tamoxifen; D002245:Carbon Dioxide; C041069:carboxyl radical; D004958:Estradiol