臺灣博碩士論文加值系統

腎上腺在減輕熱緊迫的負面影響及維持動物的能量平衡扮演重要的角色。本研究的目的為探討急性熱緊迫對L2品系台灣土雞公雞腎上腺蛋白質表現及組蛋白修飾之影響，作為了解雞耐熱力分子機制的基礎。本研究使用192隻30週齡L2品系台灣土雞公雞進行38°C及相對溼度55%之急性熱緊迫四小時，依加熱後及加熱前的體溫變化(ΔT)分成抵抗組(ΔT ≤ 2.5°C)與敏感組(ΔT ≥ 6.5°C)，熱緊迫期間死亡雞隻則定義為死亡組，另取5隻公雞飼養於25°C及相對溼度55%之氣候室作為對照組。各組選取五隻雞採腎上腺供蛋白質表現及組蛋白修飾分析，分別使用同重元素相對和絕對定量(iTRAQ)法及免標定數據依賴擷取模式(data-dependent acquisition, DDA)搭配液相層析串聯質譜儀(LC-MS/MS)獲取資料。iTRAQ分析結果顯示，在所有鑑定到的5,255個蛋白質中有140個蛋白質表現量具顯著之組間差異；基因註解分析結果顯示差異表現蛋白質主要參與細胞過程、生物調節及刺激的反應。功能路徑分析顯示，急性熱緊迫可能導致腎上腺能量失衡，增加細胞凋亡，進而改變公雞的生理狀態。熱緊迫處理組上調熱緊迫蛋白質表現，而抵抗組雞隻HSPB8、HSP70及HSP105則沒有改變。急性熱緊迫使fatty-acid amide hydrolase (FAAH)表現量上升，somatostatin (STT)在敏感組及死亡組表現量下降。抵抗組雞隻之FAAH及parathymosin表現量顯著低於敏感組者；STT、steroidogenic acute regulatory protein、hydroxy-delta-5-steroid dehydrogenase、3 beta- and steroid delta-isomerase 1及prostaglandin E synthase 3表現量則提高。腎上腺組蛋白修飾分析共定性到115個組蛋白標記，其中三甲基化組蛋白H3離胺酸27 (H3K27me3)在敏感組顯著高於其他組別(P < 0.05)。H3K27me3與基因轉錄的抑制有關，在敏感組與K36me、K36me2及K37me具有正向交聯作用。綜合以上研究結果可知，急性熱緊迫上調熱緊迫蛋白質與腎上腺皮質激素分泌相關的蛋白表現，保護雞隻腎上腺免受高溫引起的細胞凋亡，同時調控個體以免能量失衡，抵抗組雞隻較敏感組者具較高下視丘-腦下垂體-腎上腺軸反應以維持體溫之恆定；H3K27me3的改變可能與L2品系台灣土雞公雞腎上腺的耐熱性有關。

Adrenal gland plays an important role in alleviating adverse effects of heat stress and maintaining energy balance in animals. The aim of this study was to investigate the effect of acute heat stress on protein expression and histone modification in the adrenal gland of male L2 strain Taiwan country chickens as a base for understanding the molecular mechanism of thermotolerance in chickens. A total of 192 30-wk-old roosters were acute heat-stressed at 38°C and 55% relative humidity for 4 h. The roosters were grouped according to body temperature changes before and after acute heat stress (ΔT), including a resistant group with ΔT ≤ 2.5°C and sensitive group with ΔT ≥ 6.5°C. Roosters died during heat stress were defined as a dead group. Another five roosters were kept at 25°C and 55% relative humidity as a control group. The adrenal glands of five roosters in each group were collected for protein expression and histone modification analysis by using the isobaric tags for relative and absolute quantitation (iTRAQ) proteomics approach and label-free data-dependent acquisition integrated with LC-MS/MS analysis. The iTRAQ analysis showed that 140 out of 5,255 identified proteins were differentially expressed. Gene ontology analysis indicated that most of the differentially expressed proteins are involved in cellular process, biological regulation, and response to stimuli. Functional pathway analysis showed that acute heat stress induces energy imbalance, increases apoptosis and thereby may change the physiological state of the adrenal glands of roosters. Expression of heat shock proteins (HSPs) were upregulated in heat-stressed groups but there were no changes in HSPB8, HSP70 and HSP105 in the resistant group. Fatty-acid amide hydrolase (FAAH) was upregulated while somatostatin (STT) was downregulated in sensitive and dead group after acute heat stress. FAAH and parathymosin were downregulated while STT, steroidogenic acute regulatory protein, hydroxy-delta-5-steroid dehydrogenase, 3 beta- and steroid delta-isomerase 1 and prostaglandin E synthase 3 were upregulated in resistant group compared with those in sensitive group. Histone modification studies identified 115 histone marks, including tri-methylation state of histone H3 lysine 27 (H3K27me3) with significantly increased abundance in sensitive group compared to those of the other groups (P < 0.05). H3K27me3, associated with the repression of gene transcription, showed a positive crosstalk with K36me and K37me in the H3 tails of sensitive group. In conclusion, acute heat stress upregulated the expression of HSPs and corticosteroid secretion related proteins in adrenal glands, which may function as a cellular mechanisms against apoptosis and systemic response due to energy imbalance caused by acute heat stress. The resistant group showed a higher hypothalamus-pituitary-adrenal axis reactivity than that sensitive group maintaining the homeostasis of body temperature. The alteration of H3K27me3 levels were associated with the thermotolerance in the adrenal glands of male L2 Taiwan country chickens.

中文摘要……………………………………………………………………………….i
Abstract………………………………………………………………………………..ii
目錄………………………………………………………………………………...…iv
表次………………………………………………………………………………...…vi
圖次…………………………………………………………………………….…….vii
壹、 前言………………………………………………………………………………1
貳、 文獻探討…………………………………………………………………………2
一、 熱緊迫對雞隻的影響………………………………………………………2
二、 雞隻腎上腺之熱緊迫調節功能……………………………………………3
三、 表關遺傳學及組蛋白修飾(Histone post-translational modifications, HPTMs)………………………………………………………………………6
四、 蛋白質體之應用……………………………………………………………8
五、 研究目的……………………………………………………………………10
參、材料方法………………………………………………………………………11
一、試驗動物與飼養管理……………………………………………………11
二、急性熱緊迫處理及樣品採集……………………………………….….11
三、雞隻血清腎上腺素及皮質酮濃度之分析…………………………………12
四、 雞隻腎上腺蛋白質樣品製備與分析………………………………………12
(一) 腎上腺蛋白質樣品製備…………………………………….…………12
(二) 以同重元素相對和絕對定量(iTRAQ)分析雞隻腎上腺蛋白質體...12
(三) 胜肽樣品分離(Fractionation) ……………………………………….13
(四) 奈米流速級高解析液相層析-電噴灑四極棒飛行時間式串聯質譜儀(nanoUHPLC-ESI-Q-TOF-MS)………………………………………14
(五) 資料庫搜尋與蛋白質身分比對………………………...……………15
(六) 差異表現蛋白質之生物資訊分析……………………...…………...15
五、雞隻腎上腺組蛋白樣品製備與分析…………………………………….…15
(一) 腎上腺組蛋白樣品製備…………………………………….…………15
(二) 奈米流速級高解析液相層析-電噴灑四極棒飛行時間式串聯質譜儀(nanoUHPLC-ESI-Q-TOF-MS)………………………………………17
(三) 資料庫搜尋與蛋白質身分比對………………………………………18
(四) 統計分析………………………………………………………………18
肆、結果………………………………………………………………………………20
一、急性熱緊迫處理後不同組L2品系台灣土雞公雞之體溫改變……………20
二、急性熱緊迫處理後L2品系台灣土雞公雞腎上腺之差異表現蛋白質……20
三、急性熱緊迫處理後L2品系台灣土雞公雞之腎上腺差異表現蛋白質之功能註解………………………………………………………………………….20
四、以血清腎上腺素及皮質酮濃度確認急性熱緊迫處理後L2品系台灣土雞公雞之SAM軸及HPA軸活性………………………………………………………20
五、組蛋白萃取方法比較……………………………………….………………46
六、急性熱緊迫處理後L2品系台灣土雞公雞腎上腺組蛋白修飾分析………46
伍、討論……………....…………………………....………….………………………54
一、急性熱緊迫對L2品系台灣土雞公雞腎上腺蛋白質之影響…………….54
二、急性熱緊迫對抵抗組及敏感組L2品系台灣土雞公雞腎上腺蛋白質之影響……………………………………………………………………………58
三、急性熱緊迫對敏感組及死亡組L2品系台灣土雞公雞腎上腺蛋白質之影響……………………………………………………………………………62
四、急性熱緊迫對L2品系台灣土雞公雞腎上腺組蛋白修飾之影響………62
五、急性熱緊迫對抵抗組及敏感組L2品系台灣土雞公雞腎上腺蛋白質及組蛋白修飾之影響………………………………………………………………64
陸、結論…………….……………………………………………………….………67
柒、參考文獻……………………………………………….…...……………………68

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