The endogenous estrogen metabolite 2-methoxyestradiol induces apoptotic neuronal cell death in vitro.
We examined the effects of 2-methoxyestradiol, a metabolite of estradiol, on cell death in retinoic acid (RA)-differentiated neuroblastoma SH-SY5Y cell cultures. Cell death was induced by 2-methoxyestradiol in a concentration-dependent manner. Estradiol and 2-methoxyestradiol failed to induce cell death. The cell death response to 2-methoxyestradiol was sensitive to the protein synthesis inhibitor cycloheximide and the apopain inhibitor Ac-Asp-Glu-Val-Asp-H(aldehyde). 2-Methoxyestradiol also induced internucleosomal for and endogenous neuroactive steroid metabolite in the etiology of some neurodegenerative diseases.
Nakagawa-Yagi
Y
Y
Laboratory of Neurochemistry, Snow Brand Milk Products, Tochigi, Japan.
Ogane
N
N
Inoki
Y
Y
Kitoh
N
N
D000077584:2-Methoxyestradiol; D000595:Amino Acid Sequence; D017209:Apoptosis / Q000502:physiology*; D002454:Cell Differentiation / Q000187:drug effects; D003513:Cycloheximide / Q000494:pharmacology; D004958:Estradiol / Q000031:analogs & derivatives* / Q000502:physiology; D006801:Humans; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008969:Molecular Sequence Data; D009447:Neuroblastoma / Q000201:enzymology / Q000473:pathology; D009474:Neurons / Q000473:pathology*; D014212:Tretinoin / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D004958:Estradiol; D014212:Tretinoin; D000077584:2-Methoxyestradiol; D003513:Cycloheximide; D007770:L-Lactate Dehydrogenase