Moonlighting function of glycerol kinase causes systems-level changes in rat hepatoma cells.
Moonlighting function of glycerol kinase causes systems-level changes in rat hepatoma cells.
复制标题
甘油激酶的兼职功能引起大鼠肝癌细胞的系统水平变化。
DOI：
10.1016/j.ymben.2010.04.001
复制
发表时间：
2010
影响因子：
8.4
通讯作者：
Dipple,KatrinaM
中科院分区：
文献类型：
--
作者：
Sriram,Ganesh;Parr,LillyS;Rahib,Lola;Liao,JamesC;Dipple,KatrinaM
甘油激酶 (GK) 是一种具有多种（兼职）细胞功能的酶。 GK 过度表达显着影响中枢代谢通量；因此，为了阐明这些变化的机制，我们对 H4IIE 大鼠肝癌细胞中 GK 过度表达进行了系统水平评估。微阵列分析揭示了代谢中基因（中心碳和脂质）的表达改变，这与之前的通量分析相关，以及受糖皮质激素受体（GR）调节的基因的表达改变。油红O染色显示GK过度表达导致H4IIE细胞中脂肪储存增加。网络成分分析表明，过氧化物酶体增殖物激活受体 α、GR 和其他 7 个转录因子的活性因 GK 过度表达而改变。在存在或不存在糖皮质激素激动剂地塞米松的情况下，通过 GR 响应基因的定量 RT-PCR 实验验证了 GR 活性的增加。这种系统生物学方法进一步强调了 GK 在中枢和脂质代谢中的重要作用，并通过实验验证了 GK 影响 GR 转录因子活性的替代（兼职）功能。
Glycerol kinase (GK) is an enzyme with diverse (moonlighting) cellular functions. GK overexpression affects central metabolic fluxes substantially; therefore, to elucidate the mechanism underlying these changes, we employed a systems-level evaluation of GK overexpression in H4IIE rat hepatoma cells. Microarray analysis revealed altered expression of genes in metabolism (central carbon and lipid), which correlated with previous flux analysis, and of genes regulated by the glucocorticoid receptor (GR). Oil Red O staining showed that GK overexpression leads to increased fat storage in H4IIE cells. Network component analysis revealed that activities of peroxisome proliferator-activated receptor α, GR, and seven other transcription factors were altered by GK overexpression. The increased activity of GR was experimentally verified by quantitative RT-PCR of GR-responsive genes in the presence and absence of the glucocorticoid agonist, dexamethasone. This systems biology approach further emphasizes GK's essential role in central and lipid metabolism and experimentally verifies GK's alternative (moonlighting) function of affecting GR transcription factor activity.