The influence of intermittent hypobaric hypoxia on the brain iron metabolism in adult Sprague dawley

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Objective:Iron is an essential element in all living organisms and is required as a cofactor for oxygen-binding proteins.Iron metabolism,oxygen homeostasis and erythropoiesis are consequently strongly interconnected.In mammalian cells,exposure to a low-oxygen environment triggers a hypoxic response pathway centered on the regulated expression of the hypoxia-inducible transcription factor(HIF).Hypoxia has been shown to increase the expression of a variety of proteins involved in iron homeostasis.However,little is known about brain iron metabolism after intermittent hypobaric hypoxia(IHH)treatment.In this study,adult Sprague dawley(SD)rats were treated with IHH for 28 days,8h per day and then we detected iron homeostasis in different brain areas of SD rats.Results:The protein level of hippocampus transferrin receptor 1(TfR1),divalent metal transporter 1(DMT1)with IRE,DMT1(-IRE),ferritin-H,iron regulatory protein(IRP)2 and ceruloplasmin(CP)is elevated significantly while ferritin-L decreased.We have also found the down regulation of IRP1.We observe the same results in the cerebral cortex in the brain.Conclusions:We first discover that IHH has an influence on the brain iron homeostasis and the decreased ferritin-L corresponds to the down regulation of IRP1 indicating hypoxia can affect the expression of ferritin-L through IRE/IRP system.Although there is a marked increase in TfR1 expression that would lead to the raised level of LIP in cells.It can finally result in the higher ROS which can damage the cells.The concerned mechanisms involved in it remain to be deliberated. Objective: Iron is an essential element in all living organisms and is required as a cofactor for oxygen-binding proteins. Iron metabolism, oxygen homeostasis and erythropoiesis are strongly strongly interconnected. In mammalian cells, exposure to a low-oxygen environment triggers a hypoxic response Path centered on the regulated expression of the hypoxia-inducible transcription factor (HIF). Hypoxia has been shown to increase the expression of a variety of proteins involved in iron homeostasis. However, little is known about brain iron metabolism after intermittent hypobaric hypoxia (IHH ). In treatment of this study, adult Sprague Dawley (SD) rats were treated with IHH for 28 days, 8h per day and then we detected iron homeostasis in different brain areas of SD rats. Results: The protein level of hippocampus transferrin receptor 1 ( TfR1), divalent metal transporter 1 (DMT1) with IRE, DMT1 (-IRE), ferritin-H, iron regulatory protein (IRP) 2 and ceruloplasmin (CP) is significantly increased while ferritin-L decrea sed.We have also found the down regulation of IRP1.We observe the same results in the cerebral cortex in the brain.Conclusions: We first discover that IHH has an influence on the brain iron homeostasis and the decreased ferritin-L correspond to the down regulation of IRP1 indicating hypoxia can affect the expression of ferritin-L through IRE / IRP system. Although there is a marked increase in TfR1 expression that would lead to the raised level of LIP in cells. At can finally result in the higher ROS which can damage the cells. The concerned mechanisms involved in it remain to be deliberated.
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