Effect of deferiprone on expression of iron transmembrane transport protein in hippocampus of cerebral ischemia-reperfusion rats
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Key Laboratory of Hunan Province for Integrated Traditional Chinese and Western Medicine on Prevention and Treatment of Cardio-Cerebral Diseases, Hunan University of Chinese Medicine, Changsha, Hunan 410208, China)

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R363.1

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    Abstract:

    Aim To investigate the effects of deferiprone (DFP) on expressions of iron transmembrane transport proteins concluding iron influx and efflux system in the hippocampus of cerebral ischemia-reperfusion rats. Methods The rats (n=48) were randomly divided into sham operation group, cerebral ischemia-reperfusion group (I/R group) and DFP+I/R group. All rats were pretreated by intragastric administration (ig) 1 h before the middle cerebral artery occlusion method for preparing cerebral ischemia-reperfusion model. After the operation, continuous ig administration was performed for days. After cerebral ischemia-reperfusion for 72 hours, the behavioral activity of rat was recorded by Longa's neurobehavioral score standard. Iron accumulation in the hippocampus was measured by DAB-intensified Perl's histochemical staining. Western blot was used to detect the expressions of iron transmembrane transport protein in hippocampus of rats in each group, including iron importin:transferrin receptor (TFR) and divalent metal ion transporter 1 (DMT1), iron exportin:ferroportin (Fpn), hephaestin (Heph), feline leukemia virus subgroup C receptor (FLVCR) and breast cancer resistance protein (BCRP). Results Compared with I/R group, the Longa's neurobehavioral score was significantly decreased (P<0.01), the number of aggregated iron particles was reduced, the protein expressions of TFR and DMT1 were significantly decreased (P<0.05 or P<0.01), and the protein expressions of Heph, FLCVR and BCRP were up-regulated (P<0.05 or P<0.01), in the DFP+I/R group. Conclusions Deferiprone can reduce the expressions of iron importin TFR and DMT1, increase the expressions of iron exportin Heph, FLVCR and BCRP, promote the efflux of heme iron and non-heme iron and reduce brain iron deposition. Thus it can decrease nerve damage after cerebral ischemia-reperfusion and improve the disease prognosis.

    Reference
    [1] Birben E, Sahiner UM, Sackesen C, et al.Oxidative stress and antioxidant defense.WAO Journal, 2,5(1):9-19.
    [2] Bonaventura A, Liberale L, Vecchié A, et al.Update on inflammatory biomarkers and treatments in ischemic stroke.Int J Mol Sci, 6,7(12):1 967.
    [3] Liao J, Xia X, Wang GZ, et al.Naotaifang extract treatment results in increased ferroportin expression in the hippocampus of rats subjected to cerebral ischemia.Mol Med Rep, 5,1(6):4 047-052.
    [4] Ding H, Yan CZ, Shi H, et al.Hepcidin is involved in iron regulation in the ischemic brain.PLoS One, 1,6(4):471-488.
    [5] Mobarra N, Shanaki M, Ehteram H, et al.A review on iron chelators in treatment of iron overload syndromes.Int J Hematol Oncol Stem Cell Res, 6,0(4):239-247.
    [6] 黄娟, 廖君, 彭熙炜, 等.脑泰方对脑缺血/再灌注大鼠海马区Nrf2、HO-1和膜铁转运辅助蛋白表达的影响.中国药理学通报, 7,3(10):1 467-472.
    [7] 龚哲, 张晓旎, 李红红, 等.羟基红花黄素A对脑缺血再灌注后缺血半暗带自噬活性的调节作用.中国病理生理杂志, 7,3(3):449-454.
    [8] Longa EZ, Weinstein PR, Carlson S, et al.Reversible middle cerebral artery occlusion without craniectomy in rats.Stroke, 9,0(1):84-91.
    [9] Salvador GA.Iron in neuronal function and dysfunction.Biofactors, 0,6(2):103-110.
    [10] Hadzhieva M, Kirches E, Mawrin C.Review:Iron metabolism and the role of iron in neurodegenerative disorders.Neuropathol Appl Neurobiol, 4,0(3):240-257.
    [11] Rishi G, Wallace DF, Subramaniam VN.Hepcidin:Regulation of the master iron regulator.Biosci Rep, 5,5(3):e00 192.
    [12] Khan AA, Quigley JG.Heme and FLVCR-related transporter families SLC48 and SLC49.Mol Aspects Med, 3,4(2-3):669-682.
    [13] Burkhart A, Skjrringe T, Johnsen KB, et al.Expression of iron-related proteins at the neurovascular unit supports reduction and reoxidation of iron for transport through the blood-brain barrier.Mol Neurobiol, 6,3(10): 7 237-253.
    [14] Jiang R, Hua C, Wan Y, et al.Hephaestin and ceruloplasmin play distinct but interrelated roles in iron homeostasis in mouse brain.J Nutr, 5,5(5):1 003-009.
    [15] De Domenico I, Ward DMV, di Patti MCB, et al.Ferroxidase activity is required for the stability of cell surface ferroportin in cells expressing GPI-ceruloplasmin.EMBO J, 7,6(12):2 823-831.
    [16] Du F, Fan M, Gong Q, et al.Effects of hypoxic preconditioning on the expression of iron influx and efflux proteins in primary neuron culture.Neurochem Int, 2,0(4):335-343.
    [17] 廖君, 陈懿, 夏兴, 等.大鼠脑缺血后海马CA2区FLVCR和BCRP的表达及益气活血法干预.中国动脉硬化杂志, 4,2(11):1 091-096.
    [18] Latundedada GO, Laftah AH, Masaratana P, et al.Expression of ABCG2 (BCRP) in mouse models with enhanced erythropoiesis.Front Pharmacol, 4,5:135.
    [19] 康传杰, 张相彤, 马威.细胞铁死亡发生与调控机制的研究进展.中国病理生理杂志, 7,3(3):567-571.
    [20] García-Yébenes I, Sobrado M, Moraga A, et al.Iron overload, measured as serum ferritin, increases brain damage induced by focal ischemia and early reperfusion.Neurochem Int, 2,1(8):1 364-369.
    [21] Mittal S, Agarwal P, Wakhlu A, et al.Anaemia in systemic lupus erythematosus based on iron studies and soluble transferrin receptor levels.J Clin Diagn Res, 6,0(6):EC08-EC11.
    [22] Enculescu M, Metzendorf C, Sparla R, et al.Modelling systemic iron regulation during dietary iron overload and acute inflammation:Role of hepcidin-independent mechanisms.PLoS Comput Biol, 7,3(1):e1 005 322.
    [23] 廖君, 杨梅, 石咏梅, 等.益气活血中药脑泰方对脑缺血后海马CA2区铁跨膜转运蛋白表达的调节作用.世界中医药, 6,1(4):592-596.
    [24] Cao H, Wang Y, Wang Q, et al.Taxol prevents myocardial ischemia-reperfusion injury by inducing JNK-mediated HO-1 expression.Pharm Biol, 6,4(3):555-560.
    [25] Bhowmik A, Ojha D, Goswami D, et al.Inositol hexa phosphoric acid (phyticacid), a nutraceuticals, attenuates iron-induced oxidative stress and alleviates liver injury in iron overloaded mice.Biomed Pharmacother, 7,7:443-450.
    [26] Bayanzay K, Alzoebie L.Reducing the iron burden and improving survival in transfusion-dependent thalassemia patients:current perspectives.J Blood Med, 6,7(1):159-169.
    [27] Sangartit W, Pakdeechote P, Kukongviriyapan V, et al.Tetrahydrocurcumin in combination with deferiprone attenuates hypertension, vascular dysfunction, baroreflex dysfunction, and oxidative stress in iron-overloaded mice.Vascul Pharmacol, 6,7:199-208.
    [28] 尹永锋, 王改青, 陈艳丽.去铁酮对大鼠脑出血后三价铁转运体及神经功能的影响.中风与神经疾病, 4,1(2):130-132.
    [29] Sripetchwandee J, Wongjaikam S, Krintratun W, et al.A combination of an iron chelator with an antioxidant effectively diminishes the dendritic loss, tau-hyperphosphorylation, amyloids-β accumulation and brain mitochondrial dynamic disruption in rats with chronic iron-overload.Neuroscience, 6,2:191-202.
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LIAO Jun, HUANG Juan, SHI Yong-Mei, YU Qing-Ping, WU Wan-Feng, WANG Guo-Zuo, GE Jin-Wen. Effect of deferiprone on expression of iron transmembrane transport protein in hippocampus of cerebral ischemia-reperfusion rats[J]. Editorial Office of Chinese Journal of Arteriosclerosis,2018,26(6):577-582.

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History
  • Received:October 23,2017
  • Revised:February 11,2018
  • Online: July 10,2018
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