臺灣博碩士論文加值系統

Target of rapamycin (TOR) signaling is a nutrient-sensing pathway and affects aging. Longevity is increased when TOR signaling is reduced. Inactivation no afterpotential E (inaE) encodes an ortholog of human diacylglycerol lipase gene in Drosophila. EP1101 which displays up-regulation of inaE extends lifespan. On the other hand, down-regulation of inaE in KG08585 shortens lifespan. Transheterozygotes of EP1101 and KG08585 restore short-lived mutant KG08585 lifespan back to wild-type levels. Overexpression of inaE and down-regulation of rdgA at the same time in Drosophila extends lifespan similar like that of individual overexpression of inaE or down-regulation of rdgA, suggesting they function through the same pathway. In addition, ubiquitious overexpression of inaE and overexpression of the dominant-negative form of S6K simultaneously also extends lifespan similar like that of overexpression of inaE alone or overexpression of the dominant-negative form of S6K alone in Drosophila. A decreased level of phosphorylated 4EBP was detected in EP1101. Together, the data imply that inaE may modulate fly lifespan through TOR signaling activity.

雷帕徾素受器(TOR) 訊息傳遞是一個會影響老化的營養路徑。當雷帕徾素受器訊息傳遞減少時， 會增加壽命。inaE為哺乳類二酸甘油酯水解酶的同源基因。在EP1101體內的inaE大量表現，使得壽命延長。另一方面，在KG08585體內的inaE表現量低，會縮短壽命。若將EP1101和KG08585配在一起，則會發現到會將原本短命的KG08585救回到和正常果蠅的壽命一樣。同時大量表現inaE，以及將rdgA的表現量降低所造成的壽命延長，會發現到比單獨只有大量表現inaE，或只有rdgA表現量降低的造成的壽命延長幅度是一樣的。由此我們推測，大量表現inaE和rdgA表現量降低所造成壽命延長，都是藉由相同路徑調控所造成的。 此外在果蠅體內，若同是大量表現inaE，以及大量表現顯性抑制的S6K所造成的壽命延長，會和單獨只有大量表現inaE，或單獨只有大量表現顯性抑制的S6K而造成的壽命延長幅度是一樣的。在果蠅體內，我們也發現到4EBP的磷酸化會降低。綜合以上的結果，大量表現inaE可能是藉由雷帕徾素受器的活性，來調控果蠅的壽命。

English abstract……………………………………………………………………....Ⅰ
Chinese abstract………………………………………………………….………..….Ⅱ
Introduction………………………………………………………………….…….…..1
Materials and methods……………………………………………………….……….4
Results………………………………………………………………………….………8
Discussion………………………………………………………………………..……19
Figures…………………………………………………………………………..…….22
Tables………………………………………………………………………….….…...48
References………………………………………………………………………..…...60

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