Analysis of Differenciation Activity of Microbial Glycolipids on Animal Cells

我们发现微生物细胞外糖脂，琥珀酰海藻糖脂（STL）诱导单核细胞分化，甘露糖赤藓糖醇脂（MEL）诱导HL-60人白血病细胞粒细胞分化。为了探讨STL诱导HL-60细胞分化的机制，我们研究了含有不同疏水脂肪酸片段的STL类似物对HL-60细胞生长和分化的影响。结果表明，STL及其类似物对HL-60细胞的作用取决于STL疏水部分的结构。我们还发现MEL是小鼠黑色素瘤B16细胞增殖的有效抑制剂。流式细胞术分析mel处理的B16细胞的细胞周期，发现细胞在亚g0 /G1期积累，这是细胞发生凋亡的标志。在诱导凋亡的MEL浓度下，B16细胞的蛋白激酶C （PKC）活性降低。此外，大鼠嗜铬细胞瘤PC12细胞暴露于MEL增强了乙酰胆碱酯酶的活性，并中断了G1期的细胞周期，导致神经突的生长和部分细胞分化。我们的研究结果表明，MEL通过erk相关的信号级联，通过c-jun基因的反激活，诱导PC12细胞的神经元分化特征，该信号级联部分重叠了NGF激活的途径。

We found that the microbial extracellular glycolipids, succinoyl trehalose lipids (STL) induced monocytic differentiation while mannosylerythritol lipids (MEL) induced granulocytic differentiation of HL-60 human leukemia cells. In order to assess the mechanism of HL-60 cell differentiation-induction by STL, we examined the effects of analogs of STL with different hydrophobic fatty acid moieties on the growth and differentiation of HL-60 cells. Our results indicated that the effects of STL and its analogs on HL-60 cells depended on the structure of the hydrophobic moiety of STL.We also showed that MEL was a potent inhibitor of the proliferation of mouse melanoma B16 cells. Flow-cytometric analysis of the cell cycle of MEL-treated B16 cells revealed the accumulation of cells in the sub-G0/G1 phase, which is hallmark of cells undergoing apoptosis. The activity of protein kinase C (PKC) was reduced in B16 cells treated with MEL at a concentration at which induced apoptosis.Furthermore, exposure of rat pherochromocytoma PC12 cells to MEL enhanced the activity of acetylcholinesterase and interrupted the cell cycle at the G1 phase, with resulting outgrowth of neurites and partial cellular differentiation. Our results suggest that MEL induces characteristics of neuronal differentiation in PC12 cells, with transactivation of the c-jun gene, via an ERK-related signal cascade that is partially overlapping the pathways activated in response to NGF.