title: Effects of alpha-lipoic acid on expression of iron transport and storage proteins in BV-2 microglia cells.
abstract: BACKGROUND
  The antioxidant properties of alpha-lipoic acid (ALA) are associated with its ability to reduce iron in cells and tissues, which is partly due to its inhibiting effect on iron uptake from transferrin and its promoting effect on iron deposition into ferritin. However, the relevant mechanisms are unknown.
  
  
  METHODS
  We therefore investigated the effects of ALA on the expression of transferrin receptor 1 (TfR1), divalent metal transporter 1 (DMT1), ferroportin 1 (Fpn1) and ferritin in BV-2 microglia cells.
  
  
  RESULTS
  We demonstrated that ALA significantly inhibited DMT1 expression, lowered ferritin-light-chain (Ft-L) and ferritin-heavy-chain (Ft-H) content, and had no effect on TfR1 and Fpn1 in BV-2 microglia cells. This indicated that the inhibiting effect of ALA on DMT1 might be one of the causes of the ALA-induced reduction in cellular transferrin-bound-iron uptake. We also demonstrated that ALA enhanced DMT1 and TfR1 expression in ferric ammonium citrate (FAC)-treated cells. FAC treatment led to a significant increase in Ft-L, Ft-H and Fpn1, and pre-treatment with ALA resulted in a further increase in the contents of Ft-L and Ft-H but not Fpn1 in cells.
  
  
  CONCLUSIONS
  ALA could up-regulate TfR1, DMT1 and ferritin expression when iron is increased outside of the cell, promoting iron deposition into ferritin by increasing cell iron uptake, and then reducing free iron both inside and outside of the cell.
authors.affiliation: Laboratory of Neuropharmacology, Fudan University School of Pharmacy, 826 Zhang Heng Road, Pu Dong, Shanghai 201203, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Chen
authors.affiliation: Laboratory of Neuropharmacology, Fudan University School of Pharmacy, 826 Zhang Heng Road, Pu Dong, Shanghai 201203, China.
authors.forename: Fei-Mi
authors.initials: FM
authors.lastname: Li
authors.affiliation: Laboratory of Neuropharmacology, Fudan University School of Pharmacy, 826 Zhang Heng Road, Pu Dong, Shanghai 201203, China.
authors.forename: Yu-Fu
authors.initials: YF
authors.lastname: Zhou
authors.affiliation: Laboratory of Neuropharmacology, Fudan University School of Pharmacy, 826 Zhang Heng Road, Pu Dong, Shanghai 201203, China.
authors.forename: Christopher
authors.initials: C
authors.lastname: Qian
authors.affiliation: Laboratory of Neuropharmacology, Fudan University School of Pharmacy, 826 Zhang Heng Road, Pu Dong, Shanghai 201203, China.
authors.forename: Juan
authors.initials: J
authors.lastname: Li
authors.affiliation: Laboratory of Neuropharmacology, Fudan University School of Pharmacy, 826 Zhang Heng Road, Pu Dong, Shanghai 201203, China.
authors.forename: Li-Rong
authors.initials: LR
authors.lastname: Jiang
authors.affiliation: Laboratory of Neuropharmacology, Fudan University School of Pharmacy, 826 Zhang Heng Road, Pu Dong, Shanghai 201203, China. Electronic address: qianzhongming@fudan.edu.cn.
authors.forename: Zhong-Ming
authors.initials: ZM
authors.lastname: Qian
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D001692:Biological Transport / Q000187:drug effects / Q000502:physiology; D027682:Cation Transport Proteins / Q000378:metabolism*; D002460:Cell Line; D005293:Ferritins / Q000378:metabolism*; D005786:Gene Expression Regulation; D007501:Iron / Q000378:metabolism*; D051379:Mice; D017628:Microglia / Q000187:drug effects / Q000378:metabolism*; D011990:Receptors, Transferrin / Q000378:metabolism*; D008063:Thioctic Acid / Q000494:pharmacology*; D000099236:Solute Carrier Family 11, Member 2
chemical_list: D000975:Antioxidants; D027682:Cation Transport Proteins; D005293:Ferritins; D007501:Iron; D011990:Receptors, Transferrin; D008063:Thioctic Acid; D000099236:Solute Carrier Family 11, Member 2; C480029:Tfrc protein, mouse
keywords: Alpha-lipoic acid (ALA); Antioxidant properties; BV-2 microglia cells; Ferric ammonium citrate (FAC); Iron transport proteins