title: Hypobaric Hypoxia Regulates Brain Iron Homeostasis in Rats.
abstract: Disruption of iron homeostasis in brain has been found to be closely involved in several neurodegenerative diseases. Recent studies have reported that appropriate intermittent hypobaric hypoxia played a protective role in brain injury caused by acute hypoxia. However, the mechanisms of this protective effect have not been fully understood. In this study, Sprague-Dawley (SD) rat models were developed by hypobaric hypoxia treatment in an altitude chamber, and the iron level and iron related protein levels were determined in rat brain after 4 weeks of treatment. We found that the iron levels significantly decreased in the cortex and hippocampus of rat brain as compared to that of the control rats without hypobaric hypoxia treatment. The expression levels of iron storage protein L-ferritin and iron transport proteins, including transferrin receptor-1 (TfR1), divalent metal transporter 1 (DMT1), and ferroportin1 (FPN1), were also altered. Further studies found that the iron regulatory protein 2 (IRP2) played a dominant regulatory role in the changes of iron hemostasis, whereas iron regulatory protein 1 (IRP1) mainly acted as cis-aconitase. These results, for the first time, showed the alteration of iron metabolism during hypobaric hypoxia in rat models, which link the potential neuroprotective role of hypobaric hypoxia treatment to the decreased iron level in brain. This may provide insight into the treatment of iron-overloaded neurodegenerative diseases. J. Cell. Biochem. 118: 1596-1605, 2017. © 2016 Wiley Periodicals, Inc.
authors.affiliation: Laboratory of Molecular Iron Metabolism, Key Laboratory of Animal Physiology, Biochemistry and Molecular Biology of Hebei Province, College of Life Science, Hebei Normal University, Shijiazhuang 050024, Hebei Province, China.
authors.forename: Yaru
authors.initials: Y
authors.lastname: Li
authors.affiliation: Laboratory of Molecular Iron Metabolism, Key Laboratory of Animal Physiology, Biochemistry and Molecular Biology of Hebei Province, College of Life Science, Hebei Normal University, Shijiazhuang 050024, Hebei Province, China.
authors.forename: Peng
authors.initials: P
authors.lastname: Yu
authors.affiliation: Laboratory of Molecular Iron Metabolism, Key Laboratory of Animal Physiology, Biochemistry and Molecular Biology of Hebei Province, College of Life Science, Hebei Normal University, Shijiazhuang 050024, Hebei Province, China.
authors.forename: Shi-Yang
authors.initials: SY
authors.lastname: Chang
authors.affiliation: Laboratory of Molecular Iron Metabolism, Key Laboratory of Animal Physiology, Biochemistry and Molecular Biology of Hebei Province, College of Life Science, Hebei Normal University, Shijiazhuang 050024, Hebei Province, China.
authors.forename: Qiong
authors.initials: Q
authors.lastname: Wu
authors.affiliation: Laboratory of Molecular Iron Metabolism, Key Laboratory of Animal Physiology, Biochemistry and Molecular Biology of Hebei Province, College of Life Science, Hebei Normal University, Shijiazhuang 050024, Hebei Province, China.
authors.forename: Panpan
authors.initials: P
authors.lastname: Yu
authors.affiliation: Laboratory of Molecular Iron Metabolism, Key Laboratory of Animal Physiology, Biochemistry and Molecular Biology of Hebei Province, College of Life Science, Hebei Normal University, Shijiazhuang 050024, Hebei Province, China.
authors.forename: Congcong
authors.initials: C
authors.lastname: Xie
authors.affiliation: Laboratory of Molecular Iron Metabolism, Key Laboratory of Animal Physiology, Biochemistry and Molecular Biology of Hebei Province, College of Life Science, Hebei Normal University, Shijiazhuang 050024, Hebei Province, China.
authors.forename: Wenyue
authors.initials: W
authors.lastname: Wu
authors.affiliation: Laboratory of Molecular Iron Metabolism, Key Laboratory of Animal Physiology, Biochemistry and Molecular Biology of Hebei Province, College of Life Science, Hebei Normal University, Shijiazhuang 050024, Hebei Province, China.
authors.forename: Baolu
authors.initials: B
authors.lastname: Zhao
authors.affiliation: Laboratory of Molecular Iron Metabolism, Key Laboratory of Animal Physiology, Biochemistry and Molecular Biology of Hebei Province, College of Life Science, Hebei Normal University, Shijiazhuang 050024, Hebei Province, China.
authors.forename: Guofen
authors.initials: G
authors.lastname: Gao
authors.affiliation: Laboratory of Molecular Iron Metabolism, Key Laboratory of Animal Physiology, Biochemistry and Molecular Biology of Hebei Province, College of Life Science, Hebei Normal University, Shijiazhuang 050024, Hebei Province, China.
authors.forename: Yan-Zhong
authors.initials: YZ
authors.lastname: Chang
mesh_terms: D000818:Animals; D001052:Apoferritins / Q000378:metabolism; D001921:Brain / Q000378:metabolism*; D027682:Cation Transport Proteins / Q000378:metabolism; D015687:Cell Hypoxia; D004195:Disease Models, Animal; D006706:Homeostasis; D000860:Hypoxia / Q000378:metabolism*; D007501:Iron / Q000378:metabolism*; D035941:Iron Regulatory Protein 1 / Q000378:metabolism*; D035942:Iron Regulatory Protein 2 / Q000378:metabolism*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D011990:Receptors, Transferrin / Q000378:metabolism; D000098742:Ferroportin; D000099236:Solute Carrier Family 11, Member 2
chemical_list: D001052:Apoferritins; D027682:Cation Transport Proteins; D007501:Iron; D035941:Iron Regulatory Protein 1; D035942:Iron Regulatory Protein 2; D011990:Receptors, Transferrin; D000098742:Ferroportin; D000099236:Solute Carrier Family 11, Member 2; C480029:Tfrc protein, mouse
keywords: CIS-ACONITASE; HYPOBARIC HYPOXIA; IRON; IRP2; L-FERRITIN