Investigating the Relationship between the Fish Polyamine Catabolic Pathways and Hypoxia Stress

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Project title

Code/計畫編號

NSC102-2313-B019-005

Translated Name/計畫中文名

探討魚類多胺類代謝途徑的調控與缺氧緊迫的關連性

Project Coordinator/計畫主持人

Han-Jia Lin

Funding Organization/主管機關

National Science and Technology Council

Department/Unit

Department of Bioscience and Biotechnology

Website

https://www.grb.gov.tw/search/planDetail?id=8107623

Year

2014

Start date/計畫起

01-08-2014

Expected Completion/計畫迄

01-07-2015

Bugetid/研究經費

1621千元

ResearchField/研究領域

漁業

"從生理學的研究顯示，減少能量消耗與減少氧化傷害是動物耐受缺氧逆境的關鍵。從多胺類的研究顯示，多胺可以透過調控蛋白質合成和調節離子通道等機制而參與了減少能量消耗相關的生理保護機制，但卻也能透過多胺的氧化降解途徑而加劇了組織在缺氧時的傷害。事實上，多胺的不正常代謝是哺乳類腦部缺氧時造成嚴重傷害的主要原因。而抑制相關代謝活動也確實能有效減緩腦部的損傷。因此，我們研判使用藥物抑制多胺的氧化代謝作用將可以增加動物在缺氧逆境中的存活率與耐受度。本計劃擬從不同的角度，深入探討斑馬魚乙醯化多胺氧化酶 (Apao) 以及精胺氧化酶 (Smo) 這兩種多胺氧化降解途徑中的關鍵酵素以及它們對於缺氧耐受能力的影響。除了進行詳細的酵素生化特性探討之外，我們也將使用基因靜默與基因轉殖等方法建立數種魚類實驗動物模式。然後利用這些動物模式，從生理與病理的角度來驗證腦部多胺氧化降解與魚類在缺氧逆境中存活率的關係。最後，我們也將嘗試使用多胺代謝調節藥物來增加斑馬魚對於缺氧逆境的耐受能力。我們預期相關的研究成果可以對於多胺氧化降解代謝的生理意義有更深入的瞭解，並且相關成果也將能夠應用在養殖漁業上，特別是用來保護對於缺氧逆境較敏感的養殖魚種。" "Physiological studies indicated that profound metabolic suppression and avoiding free-radical injury are two key abilities of hypoxia-tolerant animals. Studies of polyamine showed that polyamine may suppress cellular energy demands by regulating protein synthesis as well as ion channels’ activity, and oxidative catabolism of polyamine is the major cause of mammals’ brain injury in ischemic stress. Further, it has been proven that suppression of polyamine oxidative catabolism may attenuate brain oxidative damage caused by hypoxia. Therefore, we proposed this research project to prove that modulation of polyamine metabolism by drugs may also improve the hypoxia tolerance of zebrafish. In this project, we will study two key enzymes in zebrafish polyamine oxidative catabolism pathway, acetylpolyamine oxidase (Apao) and spermine oxidase (Smo), by multiple strategies. We will characterize the biochemical properties of these enzymes and build several animal models, in which Apao and Smo are up-regulated or down-regulated, by using gene knockdown and transgenic techniques. These animal models will be useful in further physiological or pathological studies, which may provide evident to prove the relationship between polyamine metabolism and hypoxia tolerance ability in fish. Finally, we will try to apply drugs to improve the hypoxia tolerance ability of zebrafish through modulating polyamine metabolic pathways. This study will improve our knowledge to the physiological significances of polyamine oxidative catabolism in vertebrates. Moreover, our results may also be applicable in protecting hypoxia sensitive species in aquaculture."

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Investigating the Relationship between the Fish Polyamine Catabolic Pathways and Hypoxia Stress

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