Iron overload following manganese exposure in cultured neuronal, but not neuroglial cells.
Our previous studies show that manganese (Mn) exposure inhibits aconitase, an enzyme regulating the proteins responsible for cellular iron (Fe) equilibrium. This study was performed to investigate whether Mn intoxication leads to an altered cellular Fe homeostasis in cultured neuronal or neuroglial cells as a result of disrupted Fe regulation. Our results reveal a significant increase in the expression of transferrin receptor (TfR) mRNAs and a corresponding increase in cellular 59Fe net uptake by PC12 cells, but not astrocytes, following Mn exposure. These findings suggest that alteration by Mn of cellular Fe homeostasis may contribute to Mn-induced neuronal cytotoxicity.
Division of Environmental Health Sciences, School of Public Health, Columbia University, 60 Haven Ave., B1-110, New York, NY 10032, USA. wz18@columbia.edu
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D000818:Animals; D001253:Astrocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D015870:Gene Expression / Q000187:drug effects / Q000502:physiology; D006706:Homeostasis / Q000187:drug effects / Q000502:physiology; D007501:Iron / Q000378:metabolism; D019190:Iron Overload / Q000378:metabolism*; D007504:Iron Radioisotopes / Q000493:pharmacokinetics; D008345:Manganese / Q000494:pharmacology*; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D016716:PC12 Cells; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D011990:Receptors, Transferrin / Q000235:genetics / Q000378:metabolism
D007504:Iron Radioisotopes; D012333:RNA, Messenger; D011990:Receptors, Transferrin; D008345:Manganese; D007501:Iron