Zhao Jing, Miao Junying, Zhao Baoxiang, Zhang Shangli, Yin Deling
Institute of Developmental Biology, School of Life Science, Shandong University, Jinan 250100, China.
Int J Biochem Cell Biol. 2006;38(9):1603-13. doi: 10.1016/j.biocel.2006.03.018. Epub 2006 Apr 18.
At present, vascular endothelial cell (VEC) apoptosis induced by deprivation of fibroblast growth factor-2 (FGF-2) and serum has been well studied. But how to trigger VEC apoptosis in the presence of FGF-2 and serum is not well known. To address this question, in this study, the effects of safrole oxide on angiogenesis and VEC growth stimulated by FGF-2 were investigated. The results showed that safrole oxide inhibited angiogenesis and induced VEC apoptosis in the presence of FGF-2 and serum. To understand the possible mechanism of safrole oxide acting, we first examined the phosphorylation of Akt and the activity of nitric oxide synthase (NOS); secondly, we analyzed the expressions and distributions of Fas and P53; then we measured the activity of phosphatidylcholine specific phospholipase C (PC-PLC) in the VECs treated with and without safrole oxide. The results showed that this small molecule obviously suppressed Akt phosphorylation and the activity of NOS, and promoted the expressions of Fas and P53 markedly. Simultaneously, Fas protein clumped on cell membrane, instead of homogenously distributed. The activity of PC-PLC was not changed obviously. The data suggested that safrole oxide effectively inhibited angiogenesis and triggered VEC apoptosis in the presence of FGF-2 and serum, and it might perform its functions by suppressing Akt/NOS signal pathway, upregulating the expressions of Fas and P53 and modifying the distributing pattern of Fas in VEC. This finding provided a powerful chemical probe for promoting VEC apoptosis during angiogenesis stimulated by FGF-2.
目前，由成纤维细胞生长因子-2（FGF-2）和血清剥夺诱导的血管内皮细胞（VEC）凋亡已得到充分研究。但在FGF-2和血清存在的情况下如何触发VEC凋亡尚不清楚。为了解决这个问题，在本研究中，研究了氧化黄樟素对FGF-2刺激的血管生成和VEC生长的影响。结果表明，在FGF-2和血清存在的情况下，氧化黄樟素抑制血管生成并诱导VEC凋亡。为了解氧化黄樟素作用的可能机制，我们首先检测了Akt的磷酸化和一氧化氮合酶（NOS）的活性；其次，分析了Fas和P53的表达及分布；然后测量了用和未用氧化黄樟素处理的VEC中磷脂酰胆碱特异性磷脂酶C（PC-PLC）的活性。结果表明，这种小分子明显抑制Akt磷酸化和NOS活性，并显著促进Fas和P53的表达。同时，Fas蛋白聚集在细胞膜上，而不是均匀分布。PC-PLC的活性没有明显变化。数据表明，氧化黄樟素在FGF-2和血清存在的情况下有效抑制血管生成并触发VEC凋亡，其可能通过抑制Akt/NOS信号通路、上调Fas和P53的表达以及改变VEC中Fas的分布模式来发挥其功能。这一发现为促进FGF-2刺激的血管生成过程中的VEC凋亡提供了一个有力的化学探针。
