title: (Z)-ligustilide increases ferroportin1 expression and ferritin content in ischemic SH-SY5Y cells.
abstract: The mechanisms involved in the antioxidant and anti-apoptotic properties of (Z)-ligustilide (LIG) are not fully elucidated. Based on the accumulated data, we hypothesized that LIG might be able to reduce ischemia/reperfusion-induced increase in brain iron by regulating expression of iron transport proteins. We therefore investigated the effects of LIG on iron uptake protein transferrin receptor 1, iron exporter protein ferroportin 1, iron storage protein ferritin light chain and also hypoxia inducible factor-1 alpha (HIF-1 alpha) in oxygen-glucose deprivation/reoxygenation (OGD/R)-treated SH-SY5Y cells, using Western blot analysis. We demonstrated that LIG completely reversed the OGD/R-induced reduction of ferroportin 1, increased ferritin light chain content, and also suppressed the OGD-induced increase in HIF-1 alpha in SH-SY5Y cells. These findings imply that LIG might reduce the OGD/R-induced increase in brain iron by promoting cell iron release and iron corporation into ferritin, and also by inhibiting the HIF-1 alpha-induced increase in transferrin-bound iron uptake and iron accumulation in the brain, consequently attenuating iron-mediated free radical formation, oxidative stress and apoptosis.
authors: Laboratory of Neuropharmacology, Fudan University School of Pharmacy, Shanghai 201203, PR China.
authors: Yun-Ting
authors: YT
authors: Zhang
authors: Laboratory of Neuropharmacology, Fudan University School of Pharmacy, Shanghai 201203, PR China; School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, NT, Hong Kong.
authors: Fei-Mi
authors: FM
authors: Li
authors: Laboratory of Neuropharmacology, Fudan University School of Pharmacy, Shanghai 201203, PR China.
authors: Yi-Zhen
authors: YZ
authors: Guo
authors: Laboratory of Neuropharmacology, Fudan University School of Pharmacy, Shanghai 201203, PR China.
authors: Li-Rong
authors: LR
authors: Jiang
authors: Laboratory of Neuropharmacology, Fudan University School of Pharmacy, Shanghai 201203, PR China; School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, NT, Hong Kong.
authors: Juan
authors: J
authors: Ma
authors: School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, NT, Hong Kong. Electronic address: yake@cuhk.edu.hk.
authors: Ya
authors: Y
authors: Ke
authors: Laboratory of Neuropharmacology, Fudan University School of Pharmacy, Shanghai 201203, PR China. Electronic address: qianzhongming@fudan.edu.cn.
authors: Zhong-Ming
authors: ZM
authors: Qian
mesh_terms: D015107:4-Butyrolactone / Q000031:analogs & derivatives* / Q000494:pharmacology; D015703:Antigens, CD / Q000378:metabolism; D001052:Apoferritins / Q000378:metabolism*; D002545:Brain Ischemia / Q000473:pathology*; D027682:Cation Transport Proteins / Q000378:metabolism*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D015536:Down-Regulation / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects*; D005947:Glucose / Q000378:metabolism; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology*; D010100:Oxygen / Q000378:metabolism; D011990:Receptors, Transferrin / Q000378:metabolism; D000098742:Ferroportin
chemical_list: D015703:Antigens, CD; C068126:CD71 antigen; D027682:Cation Transport Proteins; C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D018696:Neuroprotective Agents; D011990:Receptors, Transferrin; D000098742:Ferroportin; C027820:ligustilide; D001052:Apoferritins; D005947:Glucose; D015107:4-Butyrolactone; D010100:Oxygen
keywords: (Z)-ligustilide (LIG); Antioxidant and anti-apoptosis; Hypoxia inducible factor-1 alpha (HIF-1 alpha); Iron metabolism proteins; Oxygen-glucose deprivation/reoxygen (OGD/R); SH-SY5Y cells