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Please use this identifier to cite or link to this item: http://ntour.ntou.edu.tw:8080/ir/handle/987654321/48718

Title: HIF1α在胚胎時期的造血過程中對於鐵離子恆定所扮演的角色
HIF1α regulates iron homeostasis during zebrafish embryonic hematopoiesis
Authors: Chiu, Kun-Tong
邱坤銅
Contributors: 國立臺灣海洋大學:生命科學暨生物科技學系
Keywords: 低氧誘發調控子;血基質;;運鐵蛋白;運鐵蛋白細胞接受器;斑馬魚;胚胎;初期紅血球
hypoxia inducible factor;heme;iron;transferrin;transferrin receptor;zebrafish;primitive erythropoiesis
Date: 2014
Issue Date: 2018-08-22T06:30:41Z
Abstract: 鐵離子是生物體不可或缺的元素,體內的鐵最多被用來做成hemoglobin供給紅血球的生成(Erythropoiesis),hemoglobin由各兩個α、β 次單元所組成,而hemoglobin中的heme帶有鐵離子,是紅血球攜帶氧氣的主要分子。在低氧環境下,Hypoxia-inducible factors (HIFs)是負責協助適應逆境的主要基因調控子。正常的情形之下, HIF會受到prolyl hydroxylases (PHDs)的調控經由VHL的作用而走向蛋白降解的命運,但是在缺氧或缺鐵的時候,PHDs無法對HIF作用,使得HIF能夠逐漸累積下來,促進下游基因的表現。HIF參與了許多細胞生理反應,其中對於紅血球生成的影響甚大。然而,我們對於在常氧環境下的紅血球生成過程中HIF是否對鐵離子的吸收平衡有調控作用尚不清楚。本實驗利用斑馬魚(Danio rerio)來探討HIF在胚胎發育時期紅血球造血過程中與鐵離子相關基因間的關聯。在本實驗中以RNA原位雜交分析,發現胚胎內運鐵蛋白(Transferrin)基因並未受到HIF的調控;但運鐵蛋白受體(Transferrin receptor) 則受到HIF的調控,顯示HIF確實有可能在胚胎時期,藉由調控Transferrin receptor來影響紅血球生成。
Hemoglobin is composed of two alpha and two beta subunits and each hemoglobin subunit contains a heme group. In each heme group, it contains an iron atom for oxygen transportation. The erythrocyte production and iron uptake can be induced under hypoxia environment through hypoxia-inducible factors (HIFs). The HIF alpha subunits are stabilized under hypoxia stress, which in turn associate with HIF beta subunits and activate a number of hypoxia-response genes, including the transferrin receptor and other erythrocyte-specific genes. It is unclear whether the HIFs are required for the process of erythropoiesis during development. Here we demonstrated that HIF1α plays critical functions in primitive erythropoiesis and iron uptake during embryonic erythropoiesis. Depletion of hif1α abrogated erythrocyte transferrin receptor tfr1a expression and inhibited hemoglobin hbae1 transcription. Furthermore, hypoxia treatment induced tfr1a transcription and enhanced red cell production. gata1 knockdown elicited similar phenotype with decreased tfr1a and hbae1 expression, indicating the HIF1α involves in iron uptake and utilization during primitive erythropocyte development through the regulation of Gata1. In conclusion, this study revealed that the HIF1α does not only act as a stress-response regulator to mediate organism against hypoxia impairs, it also plays fundamental functions in the process of erythrocyte development. In addition, I have demonstrated that the regulation of tfr1a by HIF1α is mediated through the Gata1 transcription factor. It is noteworthy that the transferrin (tfa) gene is not hypoxia-inducibe and its transcription is not mediated by HIF1α in the embryos.
URI: http://ethesys.lib.ntou.edu.tw/cgi-bin/gs32/gsweb.cgi?o=dstdcdr&s=G0010036046.id
http://ntour.ntou.edu.tw:8080/ir/handle/987654321/48718
Appears in Collections:[生命科學暨生物科技學系] 博碩士論文

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