17beta-estradiol protects oligodendrocytes from cytotoxicity induced cell death.
During pregnancy, changes in circulating levels of hormones, including estrogens, correlates with a significant decrease in the relapse incidence in women with Multiple Sclerosis (MS). In the present study, we demonstrate that both primary and cell line cultures of rat oligodendrocytes express the estrogen receptor (ER)-alpha and ERbeta estrogen receptors in the cytosol and nucleus, and that nuclear compartmentalization becomes more pronounced as the cells mature. Moreover, 17beta-estradiol significantly decreases the cytotoxic effects of the peroxynitrite generator 3-(4-morpholinyl)-sydnonimine (SIN-1) in both immature and mature oligodendrocytes in a dose dependent manner. This protective mechanism requires pretreatment with 17beta-estradiol and is blocked by ICI 182,780, a selective ERalpha/ERbeta antagonist. These results strongly suggest that 17beta-estradiol protects oligodendrocytes against SIN-1 mediated cytotoxicity through the activation of the estrogen receptors and provides new insights into the roles of the estrogen signaling pathways in myelin forming cells that are lost in demyelinating disorders.
Takao
Toshihiro
T
Second Department of Internal Medicine, Kochi Medical School, Nankoku, Japan.
Flint
Nicole
N
Lee
Lan
L
Ying
Xiaoyou
X
Merrill
Jean
J
Chandross
Karen J
KJ
D000818:Animals; D002451:Cell Compartmentation; D016923:Cell Death / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002467:Cell Nucleus / Q000378:metabolism; D002478:Cells, Cultured; D019610:Cytoprotection / Q000187:drug effects; D003600:Cytosol / Q000378:metabolism; D004958:Estradiol / Q000031:analogs & derivatives* / Q000494:pharmacology*; D004965:Estrogen Antagonists / Q000494:pharmacology; D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D005260:Female; D000077267:Fulvestrant; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008297:Male; D008981:Molsidomine / Q000031:analogs & derivatives / Q000633:toxicity; D020030:Nitric Oxide Donors / Q000633:toxicity; D009836:Oligodendroglia / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011960:Receptors, Estrogen / Q000235:genetics / Q000378:metabolism
D004965:Estrogen Antagonists; D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D020030:Nitric Oxide Donors; D012333:RNA, Messenger; D011960:Receptors, Estrogen; D000077267:Fulvestrant; D004958:Estradiol; C002385:linsidomine; D008981:Molsidomine; D007770:L-Lactate Dehydrogenase