Hypoxic preconditioning increases iron transport rate in astrocytes |
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Authors: | Lei Yang Ming FanFang Du Qi GongZheng Gang Bi Zhou Jing ZhuLing Ling Zhu Ya Ke |
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Institution: | a School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, NT, Hong Kongb The First Hospital, Harbin Medical University, Harbin 150081, PR Chinac Institute of Basic Medical Science, Academy of Military Medical Science, Beijing, 100850 PR China |
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Abstract: | The mechanisms involved in the neuroprotection induced by hypoxic preconditioning (HP) have not been fully elucidated. The involvement of hypoxia-inducible factor-1 alpha (HIF-1alpha) in such neuroprotection has been confirmed. There is also evidence showing that a series of genes with important functions in iron metabolism, including transferrin receptor (TfR1) and divalent metal transporter 1 (DMT1), are regulated by HIF-1alpha in response to hypoxia in extra-neural organs or cells. We therefore hypothesized that HP is able to affect the expression of iron metabolism proteins in the brain and that changes in these proteins induced by HP might be associated with the HP-induced neuroprotection. We herein demonstrated for the first time that HP could induce a significant increase in the expression of HIF-1alpha as well as iron uptake (TfR1 and DMT1) and release (ferroportin1) proteins, and thus increase tansferrin-bound iron (Tf-Fe) and non-transferrin-bound iron (NTBI) uptake and iron release in astrocytes. Moreover, HP could lead to a progressive increase in cellular iron content. We concluded that HP has the ability to increase iron transport speed in astrocytes. Based on our findings and the importance of astrocytes in neuronal survival in hypoxic/ischemic preconditioning, we proposed that the increase in iron transport rate and cellular iron in astocytes might be one of the mechanisms associated with the HP-induced neuroprotection. We also demonstrated that ferroportin1 expression was significantly affected by HIF-1alpha in astrocytes, implying that the gene encoding this iron efflux protein might be a hypoxia-inducible one. |
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Keywords: | Hypoxic preconditioning (HP) Neuroprotection Transferrin receptor (TfR1) Divalent metal transporter 1 (DMT1) Ferroportin1 (Fpn1) Hypoxia-inducible factor-1 alpha (HIF-1alpha) |
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