Corticosterone induces dysregulation of iron metabolism in hippocampal neurons in vitro.
Iron is required for neuronal function but in excess generates neurodegeneration. Although the iron homeostasis machinery in neurons has been described extensively, little is known about the influence of corticosterone on the iron homeostasis in neurons. In this study, we characterized the response of hippocampal neurons to a model of progressive corticosterone condition. We found that increasing extracellular corticosterone-induced iron accumulation killed a large proportion of neurons. Iron concentrations were significantly increased in the corticosterone-treated cells. In the hippocampal neurons, corticosterone decreased expression of ferritin and increased expression of transferrin receptor1 (TfR1), iron regulatory protein1 (IRP1), and divalent metal transporter 1. Corticosterone-induced elevation of IRP1 expression can cause increase of TfR1 and decrease of ferritin expression, which further leads to iron accumulation in hippocampal neurons and subsequently increases the oxidative damage of the neurons; it is indicated that corticosterone might be an important reason for iron deposition-caused neurodegenerative diseases.
Wang
Lei
L
Department of Clinical Nutrition, General Hospital of Armed Police Forces, 69 Yongding Road, Beijing, 100039, People's Republic of China.
Wang
Huanyu
H
Li
Li
L
Li
Wei
W
Dong
Xiaoman
X
Li
Min
M
Lv
Li
L
D000818:Animals; D027682:Cation Transport Proteins / Q000378:metabolism; D016923:Cell Death; D002478:Cells, Cultured; D003345:Corticosterone / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006624:Hippocampus / Q000378:metabolism*; D007501:Iron / Q000378:metabolism*; D035941:Iron Regulatory Protein 1 / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011990:Receptors, Transferrin / Q000378:metabolism; D000098742:Ferroportin
D027682:Cation Transport Proteins; D011990:Receptors, Transferrin; C545564:Tfrc protein, rat; D000098742:Ferroportin; D007501:Iron; D035941:Iron Regulatory Protein 1; D003345:Corticosterone