Loss of Sphingosine Kinase Alters Life History Traits and Locomotor Function in Caenorhabditis elegans.
Loss of Sphingosine Kinase Alters Life History Traits and Locomotor Function in Caenorhabditis elegans.
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DOI：
10.3389/fgene.2017.00132
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发表时间：
2017
影响因子：
3.7
通讯作者：
Staab TA
中科院分区：
文献类型：
--
作者：
Chan JP;Brown J;Hark B;Nolan A;Servello D;Hrobuchak H;Staab TA
鞘脂代谢对于平衡参与细胞信号传导、神经元功能和存活的生物活性脂质分子的丰度是重要的。具体而言，鞘脂鞘氨醇介导细胞死亡信号，而其磷酸化形式鞘氨醇-1-磷酸（S1 P）介导细胞存活信号。鞘氨醇激酶产生S1 P，鞘氨醇激酶的活性影响细胞在压力和挑战下生存的能力。为了研究鞘脂代谢的影响，特别是调节鞘氨醇和S1 P的酶，在介导衰老，神经元功能和应激反应，我们研究了生活史特征，运动能力和热应激反应的年轻和年老的动物使用的模式生物秀丽隐杆线虫。我们发现C.与野生型动物相比，缺乏鞘氨醇激酶的秀丽线虫SPHK-1突变体具有更短的寿命、减少的窝数和更小的体型。通过分析一组在鞘脂信号通路中有基因突变的年轻和年老动物，我们发现年老的sphk-1突变体在神经肌肉功能和运动行为方面表现出更大的下降。此外，缺乏sphk-1的老年动物更容易因急性和长期热暴露而死亡。另一方面，神经酰胺合酶（将鞘氨醇转化为神经酰胺）功能突变缺失的老年动物，随着年龄的增长，神经肌肉功能和应激反应表现出改善。该表型依赖于sphk-1。总之，我们的数据表明，鞘氨醇激酶的损失导致动物健康状况不佳，这表明鞘脂信号传导可能对衰老过程中健康的神经元功能和动物应激反应很重要。
Sphingolipid metabolism is important to balance the abundance of bioactive lipid molecules involved in cell signaling, neuronal function, and survival. Specifically, the sphingolipid sphingosine mediates cell death signaling, whereas its phosphorylated form, sphingosine-1-phosphate (S1P), mediates cell survival signaling. The enzyme sphingosine kinase produces S1P, and the activity of sphingosine kinase impacts the ability of cells to survive under stress and challenges. To examine the influence of sphingolipid metabolism, particularly enzymes regulating sphingosine and S1P, in mediating aging, neuronal function and stress response, we examined life history traits, locomotor capacities and heat stress responses of young and old animals using the model organism Caenorhabditis elegans. We found that C. elegans sphk-1 mutants, which lack sphingosine kinase, had shorter lifespans, reduced brood sizes, and smaller body sizes compared to wild type animals. By analyzing a panel of young and old animals with genetic mutations in the sphingolipid signaling pathway, we showed that aged sphk-1 mutants exhibited a greater decline in neuromuscular function and locomotor behavior. In addition, aged animals lacking sphk-1 were more susceptible to death induced by acute and prolonged heat exposure. On the other hand, older animals with loss of function mutations in ceramide synthase (hyl-1), which converts sphingosine to ceramide, showed improved neuromuscular function and stress response with age. This phenotype was dependent on sphk-1. Together, our data show that loss of sphingosine kinase contributes to poor animal health span, suggesting that sphingolipid signaling may be important for healthy neuronal function and animal stress response during aging.