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Title: 多胺類代謝酵素對於小鼠懷孕與胚胎發育的關係探討
Polyamine Catabolic Enzymes and Their Influences on Pregnancy Mice and Embryo
Authors: 林翰佳
Contributors: NTOU:Institute of Bioscience and Biotechnology
Date: 2008-08
Issue Date: 2011-06-28T07:17:59Z
Publisher: 行政院國家科學委員會
Abstract: 摘要:多胺類 (polyamine) 是細胞生長的必要因子,因此多胺類的合成與代 謝受到細胞嚴密地調控。當細胞內多胺類不足時會刺激多胺類合成機制, 而多胺類過多時則會啟動多胺類的相互轉換代謝機制,進行不同種類多胺 類的轉換。而在懷孕小鼠的子宮與胎盤中發現的雙胺氧化酶 (diamine oxidase),則被認為是進行多胺類代謝的另一條分支反應。 雙胺氧化酶可以催化多胺類的代謝而產生幫助胚胎發育的產物,例如 γ-胺基丁酸 (GABA) 與 β-丙氨酸 (β-alanine) 等。因此我們推測雙胺氧化 酶在懷孕與胚胎發育過程中扮演了代謝與傳遞多胺類訊息的重要角色。為 了證明這個論點,我們研擬了三個研究目標:首先我們將針對懷孕各時期 的子宮、胎盤與胎兒等組織,分析多胺類代謝相關基因的表現情形,從各 基因的表現消長瞭解多胺類的可能代謝方向;其次,我們將建立分析多胺 類代謝產物的實驗技術。由分析各組織中的多胺類種類與濃度了解相關代 謝酵素的作用;最後我們將建立基因轉殖動物模式,以誘導的方式在子宮 中或是胚胎的特定時期過量表現雙胺氧化酶,以證明雙胺氧化酶對於懷孕 與胚胎發育的重要性。 目前的初步成果顯示雙胺氧化酶在子宮與胎盤中的表現,從懷孕中期 之後就逐漸下降;反而在胎兒中的表現到了懷孕末期突然上升。這樣的結 果顯示雙胺氧化酶的作用於懷孕過程不斷的進行動態的調整,我們推測雙 胺氧化酶的代謝作用很可能是多胺類訊息作用的一種重要方式,負責維持 正常的懷孕過程。
Abstract:Polyamines are essential molecules for the normal growth of cells. Both the synthetic and catabolic pathways of polyamines are under restricted control. The pool of each polyamine in cells maintains homeostasis. The synthetic mechanism will be stimulated when cellular polyamine decreased. The interconversion reaction will be activated to convert different types of polyamine between them while a specific type of polyamine exceeded. Meanwhile, diamine oxidase, found abundantly in pregnant uterus and placenta, is able to metabolize polyamine in a branched pathway. Diamine oxidase is able to oxidize polyamines. Some of the reaction’s products, such as gamma-amino butyric acid (GABA) and β-alanine, are known as beneficial factors for embryonic development. Hence, we suggest that diamine oxidase is a key enzyme to deliver the signal from polyamine and play a role to maintain pregnancy procedure. To prove our hypothesis, three specific aims were proposed. Firstly, we would like to monitor the gene expression patterns of polyamine catabolic enzymes in uterus, placenta and embryo at different pregnant stages. We could deduce the catabolic direction of polyamine in each organ through these data. Secondly, we will establish the analytic methods to determine the different types of polyamines and their metabolites. The characteristics of the polyamine metabolites in each organ are also important for understanding the usage of polyamine. Finally, we would like to use a transgenic mouse model, which is able to overexpress diamine oxidase after boosted an induction signal, to establish the importance of diamine oxidase pathway in normal pregnany procedure. Our preliminary data indicates that the expression of diamine oxidase declined in uterus and placenta after the mid-stage of pregnancy. However, the expression of diamine oxidase increased dramatically at the final stage of pregnancy. These data indicates the dynamic regulation of diamine oxidase during pregnancy that should stand for important physiological roles.
Relation: NSC97-2311-B019-002
Appears in Collections:[Department of Bioscience and Biotechnology ] Research Reports

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