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    請使用永久網址來引用或連結此文件: http://ir.lib.ncu.edu.tw/handle/987654321/6390


    題名: 在終極肌肉分化時,肌肉性bHLH轉錄因子對PGC-1α的調控;Myogenic basic helix-loop-helix transcription factors regulate PGC-1α during terminal myogenic differentiation
    作者: 黃凱民;Kai-min Huang
    貢獻者: 生命科學研究所
    關鍵詞: 過氧化物酶增殖體激活受體γ共激活蛋白1;慢速收縮肌;Stra13;PGC-1α;P/CAF;MyoD;slow-twitch muscle fiber
    日期: 2007-07-10
    上傳時間: 2009-09-22 10:18:44 (UTC+8)
    出版者: 國立中央大學圖書館
    摘要: 成熟肌肉細胞一般分為兩種型態,第一型慢速收縮肌跟第二型快速收縮肌。在慢速收縮肌中,我們發現含有大量粒線體,因此可以藉由氧化電子傳遞鏈提供大量ATP提供人體生存所需的能量,反觀,快速收縮肌在能量代謝方面比較偏向醣解代謝,在外觀上,因為慢速收縮肌含有多血紅蛋白所以比較偏向紅色。目前我們知道PPAR-γ輔助轉錄因子PGC-1α在肌肉纖維的決定上有莫大關鍵性,而成體上主要表現在慢速收縮肌中。而之前文獻指出,轉殖鼠系統中,若過量表現PGC-1α在肌肉細胞中,會使得肌肉細胞走向慢速肌肉的趨勢,從之前觀察,我們知道在PGC-1α啟動子區有兩個非常保留E-box(CANNTG),較轉錄起始點遠的E-box我們稱為E1-box,較轉錄起始點近的E-box稱為E2-box,由之前觀察我們知道MyoD 活化PGC-1α時,是藉由直接結合於PGC-1α啟動區的E2-box。藉由生物資訊分析另一個E-box是可能被Stra13所結合。從promoter assay,我們知道Stra13會抑制MyoD所主導PGC-1α的活化,而可能藉由的方式是經由跟MyoD競爭coactivator-P/CAF,而導致MyoD活化PGC-1α有所被抑制。 Skeletal muscle are generally classified as two types – type I (slow - twitch) and type II (fast - twitch). The former is rich in mitchondria and thus provides constant ATP through oxidative metabolism. The latter depends on the glycolytic metabolism as the energy source. PGC-1α is a transcriptional coactivator mainly expressed in the slow-twitch fibers. Previous studies indicated that over-expression of PGC-1α promotes the conversion from fast-twitch fibers to slow-twitch fibers. According to previous observations, we know that the E2-box on the PGC-1α promoter is essential for MyoD-mediated transactivation. In this study, we found that Stra13, a putative E1-box binding transcriptional repressor, repressed the MyoD mediated PGC-1α promoter activation. The interaction between MyoD and Stra13 was almost undetectable by GST-Pull down assay and EMSA. In addition, over-expression of P/CAF, but not CBP, can rescue the Stra13-mediated repression. These data suggest that Stra13 represses MyoD-mediated PGC-1 activation by sequestering P/CAF from MyoD.
    顯示於類別:[生命科學研究所 ] 博碩士論文

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