The iron regulatory hormone hepcidin inhibits expression of iron release as well as iron uptake proteins in J774 cells |
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| Authors: | Fang Du Zhong-ming Qian Qi Gong Zhou Jin Zhu Lina Lu Ya Ke |
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| Institution: | 1. School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, NT, Hong Kong;2. Laboratory of Neuropharmacology, School of Pharmacy Fudan University, Shanghai 201203, PRC;1. Regional Center for Neurosensory Disorders, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA;2. Department of Dental Ecology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA;3. Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA;4. National Institute of Environmental Health Sciences, Research Triangle Park, NC, USA;5. Ariadne Diagnostics LLC, Rockville, MD, USA;6. Department of Community Dentistry & Behavioral Science, University of Florida, Gainesville, FL, USA;7. Department of Oral Diagnostic Sciences, University at Buffalo, Buffalo, NY, USA;8. University of Maryland School of Dentistry, Baltimore, MD, USA;1. Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea;2. Institute of Clinical Medicine Research, Bucheon St. Mary''s Hospital, The Catholic University of Korea, Seoul, Republic of Korea;3. Department of Radiology, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea;1. Department of Medical Biophysics, The University of Western Ontario, Canada;2. Centre for Functional and Metabolic Mapping, Robarts Research Institute, The University of Western Ontario, Canada;3. Department of Medical Imaging, The University of Western Ontario, Canada;4. Department of Clinical Neurological Sciences, The University of Western Ontario, London Health Sciences Centre, University Hospital, 339 Windermere Road, London, Ontario, Canada, N6A 5A5;1. Department of Neurology, Indiana University School of Medicine, Indianapolis, IN 46202, United States;2. Department of General Surgery, Peking University People’s Hospital, Beijing 100044, China;3. School of Health Sciences, Purdue University, West Lafayette, IN 47907, United States;4. Department of Neurology, Philipps University Marburg, Marburg, Germary;5. School of Pharmaceutical Sciences, Peking University, Beijing, China |
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| Abstract: | The mechanism by which hepcidin controls cellular iron release protein ferroportin 1 (Fpn1) in macrophages has been well established. However, little is known about the effects of hepcidin on cellular iron uptake proteins. Here, we demonstrated for the first time that hepcidin can significantly inhibit the expression of transferrin receptor 1 (TfR1) and divalent metal transporter 1 in addition to Fpn1, and therefore reduce transferrin-bound iron and non-transferrin-bound iron uptake and also iron release in J774 macrophages. Analysis of mechanisms using the iron-depleted cells showed that hepcidin has a direct inhibitory effect on all iron transport proteins we examined. Further studies demonstrated that the down-regulation of TfR1 induced by hepcidin is associated with cyclic adenosine monophosphate (cAMP) and protein kinase A (PKA), probably being mediated by the cAMP–PKA pathway in J774 macrophages. |
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