Microtubule active taxanes inhibit polycystic kidney disease progression in cpk mice.
Microtubule active taxanes inhibit polycystic kidney disease progression in cpk mice.
复制标题
微管活性紫杉烷抑制 cpk 小鼠多囊肾病的进展。
DOI：
10.1038/ki.1997.222
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发表时间：
1997
影响因子：
19.6
通讯作者：
Wang,CJ
中科院分区：
文献类型：
--
作者：
Woo,DD;TabancayJr,AP;Wang,CJ
微管活性紫杉烷抑制小鼠多囊肾病进展。纯合子scpk/ cpk小鼠在4 - 5周龄时发生多囊肾病并死于尿毒症。每周接受紫杉醇治疗的Cpk/cpkmice可以活到6个月以上。这种多囊肾病进展的戏剧性缓和被认为是紫杉醇稳定微管的能力的结果。在这项研究中，不同能力的紫杉烷促进微管蛋白二聚体自发体外组装成微管的能力被测试，以抑制多囊/ cpk小鼠多囊肾病的进展。我们发现紫杉醇、10-癸烯-紫杉醇和头肌氨酸等促进微管组装的紫杉醇类化合物显著延长了多囊虫/ cpk小鼠的存活时间。相比之下，微管无活性紫杉烷baccatin-III对pk/ cpk小鼠肾功能衰竭的进展没有影响。我们得出结论，促进微管组装的能力可能是紫杉醇和相关紫杉烷调节pk/ cpk小鼠多囊肾进展的必要条件。
Microtubule active taxanes inhibit polycystic kidney disease progression incpkmice.Homozygouscpk/cpkmice develop polycystic kidney disease and die of uremia between the fourth and fifth weeks of age.Cpk/cpkmice treated weekly with paclitaxel (Taxol) can live to over six months of age. This dramatic moderation of polycystic kidney disease progression has been postulated to be a result of paclitaxel's ability to stabilize microtubules. In this study, the ability of taxanes with differing abilities to promote spontaneousin vitroassembly of tubulin dimers into microtubules were tested for their ability to inhibit the progression of polycystic kidney disease in polycysticcpk/cpkmice. We found that taxanes that are active in promoting microtubule assembly, including paclitaxel, 10-deactyl-taxol and cephalomannine increased the survival of polycysticcpk/cpkmice significantly longer than control animals. In contrast, the microtubule inactive taxane baccatin-III has no effect on the progression of renal failure incpk/cpkmice. We conclude that the ability to promote microtubule assembly may be necessary for paclitaxel and related taxanes to modulate the progression of polycystic kidney progression incpk/cpkmice.