Hexokinase is a key regulator of energy metabolism and ROS activity in insect lifespan extension.
Hexokinase is a key regulator of energy metabolism and ROS activity in insect lifespan extension.
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己糖激酶是昆虫寿命延长中能量代谢和ROS活性的关键调节因子
DOI：
10.18632/aging.100885
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发表时间：
2016-02
期刊：
影响因子：
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通讯作者：
Xu WH
中科院分区：
文献类型：
--
作者：
Lin XW;Xu WH
发育停滞(滞育)是一种类似于秀丽线虫Dauer阶段和果蝇寿命延长的“非衰老”状态。滞育导致代谢活性降低，并显著延长昆虫的寿命。在这里，我们克隆了棉铃虫HexoKinase(HK)基因，这是一个对该物种的发育停滞至关重要的基因。非滞育性蛹的HK表达和活性水平显著高于滞育性蛹。HK活性的下调通过降低代谢活性和增加ROS活性来降低细胞活力和延缓蛹的发育，这表明HK是昆虫发育的关键调节因子。然后我们鉴定了转录因子Har-CREB、-c-Myc和-Pou特异性地结合Har-HK启动子并调节其活性。有趣的是，Har-Pou和-c-Myc是HK表达的特异性转录因子，而Har-CREB是非特异性的。此外，Har-Pou和-c-Myc对上游激素蜕皮激素也有反应。因此，滞育个体的低蜕皮激素水平导致Har-Pou和-c-Myc的低表达，最终抑制Har-HK的表达，并诱导进入滞育或延长寿命。
Developmental arrest (diapause) is a ‘non-aging’ state that is similar to the Caenorhabditis elegans dauer stage and Drosophila lifespan extension. Diapause results in low metabolic activity and a profound extension of insect lifespan. Here, we cloned the Helicoverpa armigera Hexokinase (HK) gene, a gene that is critical for the developmental arrest of this species. HK expression and activity levels were significantly increased in nondiapause-destined pupae compared with those of diapause-destined pupae. Downregulation of HK activity reduced cell viability and delayed pupal development by reducing metabolic activity and increasing ROS activity, which suggests that HK is a key regulator of insect development. We then identified the transcription factors Har-CREB, -c-Myc, and -POU as specifically binding the Har-HK promoter and regulating its activity. Intriguingly, Har-POU and -c-Myc are specific transcription factors for HK expression, whereas Har-CREB is nonspecific. Furthermore, Har-POU and -c-Myc could respond to ecdysone, which is an upstream hormone. Therefore, low ecdysone levels in diapause-destined individuals lead to low Har-POU and -c-Myc expression levels, ultimately repressing Har-HK expression and inducing entry into diapause or lifespan extension.