Department of Pediatrics, University of Chicago, Chicago, IL 60637, USA.
Department of Pediatrics, University of Chicago, Chicago, IL 60637, USA.
Biochem Biophys Res Commun. 2018 Jun 7;500(3):597-602. doi: 10.1016/j.bbrc.2018.04.110. Epub 2018 Apr 23.
Sphingosine-1-phosphate is synthesized by two sphingosine kinases, cytosolic SK1 and nuclear SK2 but SK2 expression was much higher than SK1in mouse skin fibroblasts. However, in SK2 cells, SK1 expression was markedly increased to SK2 levels whereas in SK1 cells, SK2 expression was unaffected. Ceramide, glucosylceramide and sphingosine levels were all increased in SK1 but less so in SK2 cells and S1P levels were not significantly reduced in either SK1 or SK2 cells. Greatly increased Ceramide glucosyltransferase expression was observed in SK1 cells but less so in SK2 cells suggested a role in drug resistance. SK2 cells grew faster than control and SK1. The cell division gene PCNA was significantly overexpressed in SK2 cells, suggesting a cross regulation between SKs and Ceramide glucosyltransferase.
鞘氨醇-1-磷酸由两种鞘氨醇激酶(细胞质 SK1 和核 SK2)合成,但 SK2 在小鼠皮肤成纤维细胞中的表达远高于 SK1。然而,在 SK2 细胞中,SK1 的表达明显增加到 SK2 水平,而在 SK1 细胞中,SK2 的表达不受影响。鞘氨醇、葡萄糖神经酰胺和鞘氨醇水平在 SK1 中均增加,但在 SK2 细胞中增加较少,而 S1P 水平在 SK1 或 SK2 细胞中均无明显降低。在 SK1 细胞中观察到鞘氨醇葡萄糖基转移酶表达显著增加,但在 SK2 细胞中增加较少,这表明其在耐药性中起作用。SK2 细胞的生长速度快于对照和 SK1 细胞。细胞分裂基因 PCNA 在 SK2 细胞中明显过表达,表明 SKs 和鞘氨醇葡萄糖基转移酶之间存在交叉调节。