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Angiotensin II Inhibits Iron Uptake and Release in Cultured Neurons

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Abstract

Based on the well-confirmed roles of angiotensin II (ANGII) in iron transport of peripheral organs and cells, the causative link of excess brain iron with and the involvement of ANGII in neurodegenerative disorders, we speculated that ANGII might also have an effect on expression of iron transport proteins in the brain. In the present study, we investigated effects of ANGII on iron uptake and release using the radio-isotope methods as well as expression of cell iron transport proteins by Western blot analysis in cultured neurons. Our findings demonstrated for the first time that ANGII significantly reduced transferrin-bound iron and non-transferrin bound iron uptake and iron release as well as expression of two major iron uptake proteins transferrin receptor 1 and divalent metal transporter 1 and the key iron exporter ferroportin 1 in cultured neurons. The findings suggested that endogenous ANGII might have a physiological significance in brain iron metabolism.

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Abbreviations

ACE:

Angiotensin-converting enzyme

AD:

Alzheimer’s disease

ANGII:

Angiotensin II

AT1 and AT2:

Angiotensin II (ANGII) type 1 receptor and type 2 receptor

DMT1 − IRE:

Divalent metal transporter 1 without iron response element

DMT1 + IRE:

Divalent metal transporter 1 with iron response element

Fpn1:

Ferroportin 1

GFAP:

Glial fibrillary acidic protein

iNOS:

Inducible nitric oxide synthase

MAP2:

Microtubule-associated protein 2

NTBI:

Non-transferrin bound iron

PBS:

Phosphate buffered saline

PD:

Parkinson’s disease

RAS:

Renin–angiotensin system

Tf-Fe:

Transferrin-bound iron

TfR1:

Transferrin receptor 1

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Acknowledgments

The studies in our laboratories were supported by the Competitive Earmarked Grants of The Hong Kong Research Grants Council (GRF 466713), National 973 Programs (2011CB510004), the General Grant of National Natural Science Foundation of China (NSFC) (31271132-2012, 31371092-2013), Key Project Grant of NSFC (31330035-2013) and Direct Grant of the Chinese University of Hong Kong (2011.1.084).

Conflict of interest

The authors declare no conflict of interest.

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Authors and Affiliations

  1. Department of Neurology, Xin Qiao Hospital, Third Military Medical University, Chongqing, 400038, China

    Yong Liu

  2. Laboratory of Neuropharmacology and Department of Neurosurgery, South-West Hospital, Third Military Medical University, Chongqing, 400038, China

    Suna Huang, Guang Yang, Li Rong Jiang, Chao Zhang & Zhong-ming Qian

  3. School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, NT, Hong Kong

    Fang Du

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  1. Yong Liu
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  2. Suna Huang
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Correspondence to Zhong-ming Qian.

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Liu, Y., Huang, S., Du, F. et al. Angiotensin II Inhibits Iron Uptake and Release in Cultured Neurons. Neurochem Res 39, 893–900 (2014). https://doi.org/10.1007/s11064-014-1285-3

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  • DOI: https://doi.org/10.1007/s11064-014-1285-3

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