Edelfosine抑制S.pombe细胞分裂作用机制的研究  

Study of the inhibition mechanism of edelfosine on cytokinesis in Schizosaccharomyces pombe

作　　者：张辉[1] 喻莉萍[2] 方芳[1] 方云祥[1] 

机构地区：[1]中南大学湘雅医学院药理学教研室 [2]湘南学院图书馆,湖南郴州423000

出　　处：《中国药理学通报》2007年第3期374-379,共6页Chinese Pharmacological Bulletin

摘　　要：目的研究edelfosine(ET-18-OCH3,依地福新)抑制schizosaccharom yces pombe(S.pombe,粟酒裂殖酵母)细胞分裂的作用机制。方法应用胞质分裂抑制试验,平行生长抑制试验,观察edelfosine对S.pombe细胞分裂和生长的抑制作用;应用酵母基因再转染试验,探索其作用机制。结果edelfosine在低剂量浓度时,抑制S.pombe细胞分裂;高剂量时抑制其生长。平行生长抑制试验显示,删除了mid2、spm1和pmp1基因的细胞株(mid2△、spm1△和pmp1△),对高剂量edelfosine有抵抗作用;再转染了相应的基因后,细胞重新恢复了对edelfosine的敏感性。Spm1、Mid2和Pmp1相互作用的试验研究显示,Mid2介导磷酸化Spm1的生成,而Pmp1抑制磷酸化Spm1的生成。结论edelfosine可能通过影响Spm1、Mid2和Pmp1蛋白磷酸化而产生胞质抑制和生长抑制作用。Aim To study inhibition mechanism of edelfosine on cytokinesis in Schizosaccharomyces pombe. Methods To observe the inhibition of cytokinesis and growth, the experiments of inhibition of cytokinesis and parallel growth were carried out. To explore the inhibition mechanism of edelfosine, the experiment of retransfection of yeast genes was carried out. Results Edelfosine inhibited the cytokinesis of S. pombe in low dosage and cell growth in high dosage. The mid2△ ,spm1△ and pmp1△ strains were resistant to edelfosine in high dosage. However, these strains retrieved the age by retransfected sensitive to edelfosine in high dosage by retransfected the relevant genes, respectively.A reciprocal action, which was the Mid2p induced the phosphorylated Spm1, while the Pmpl dephosphorylated Spm1, existed among the Spm1 ,Mid2 and Pmp1 in S. pombe treated with edelfosine. Conclusion The inhibition of edelfosine on cytokinesis and cell growth due to the effect of Spm1 ,Mid2 and Pmp1.

关 键 词：EDELFOSINE SCHIZOSACCHAROMYCES POMBE 细胞分裂 

分 类 号：R329.24[医药卫生—人体解剖和组织胚胎学] R329.25[医药卫生—基础医学]