Estrogen protects neuronal cells from amyloid beta-induced apoptotic cell death.
Accumulating studies have shown that estrogen replacement therapy reduces the risk of Alzheimer's disease. In this study, we clarified that 17beta-estradiol (E2) significantly rescues PC12 neuronal cells from amyloid beta protein (Abeta)-induced cell death. We found that the amino acid residues of 25 to 35 (Abeta25-35) were more cytotoxic than the full length protein (Abeta1-40) and these residues induced DNA fragmentation typical for apopto- sis. In addition, E2 was confirmed to inhibit calcium influx and cytochrome c release induced by Abeta25-35. Since these sequential events cause apoptosis, the protective effect of E2 may be exerted not by the direct interaction with Abeta, but by the blockade of the mitochondrial apoptotic pathway induced by Abeta.
Hosoda
T
T
Department of Obstetrics and Gynecology, Kyoto Prefectural University of Medicine, Kawaramachi-Hirokoji, Kamikyo-ku, Kyoto, 602-8566, Japan.
Nakajima
H
H
Honjo
H
H
D000544:Alzheimer Disease / Q000188:drug therapy / Q000503:physiopathology / Q000517:prevention & control; D016229:Amyloid beta-Peptides / Q000378:metabolism / Q000633:toxicity*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D001921:Brain / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D002118:Calcium / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D003574:Cytochrome c Group / Q000378:metabolism; D053938:DNA Fragmentation / Q000187:drug effects / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D004958:Estradiol / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology*; D004965:Estrogen Antagonists / Q000494:pharmacology; D015914:Estrogen Replacement Therapy; D000077267:Fulvestrant; D007424:Intracellular Fluid / Q000187:drug effects / Q000502:physiology; D008593:Menopause / Q000378:metabolism; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D009410:Nerve Degeneration / Q000139:chemically induced / Q000188:drug therapy* / Q000503:physiopathology; D009474:Neurons / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology*; D016716:PC12 Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D010446:Peptide Fragments / Q000633:toxicity; D051381:Rats; D013629:Tamoxifen / Q000494:pharmacology
D016229:Amyloid beta-Peptides; D003574:Cytochrome c Group; D004965:Estrogen Antagonists; D018696:Neuroprotective Agents; D010446:Peptide Fragments; C113041:amyloid beta-protein (35-25); D013629:Tamoxifen; D000077267:Fulvestrant; D004958:Estradiol; D002118:Calcium