过度的Na (+) / K (+) / Cl(-)转运蛋白基因诱导细胞增殖和在小鼠成纤维细胞表型转化。

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Panet R,马库斯M,亚特兰大H

过度的Na (+) / K (+) / Cl(-)转运蛋白基因诱导细胞增殖和在小鼠成纤维细胞表型转化。

J细胞杂志。2000年1月,182 (1):109 - 18。

PubMed ID

10567922 (在PubMed

]

文摘

Na (+) / K (+) / Cl(-)转运蛋白活动刺激G(1)早期阶段的细胞周期,这刺激了在成纤维细胞细胞增殖是一个重要事件。为了进一步阐明Na的角色(+)/ K (+) / Cl(-)转运蛋白在细胞增殖,我们过表达基因编码Na (+) / K (+) / Cl(-)转运蛋白在小鼠成纤维细胞,并分析细胞表型变化。鼠标Balb / c 3 t3细胞稳定转染的互补鲨鱼直肠腺Na (+) / K (+) / Cl(-)转运蛋白基因(NKCC1),并表示在一个哺乳动物向量巨细胞病毒启动子(Balb / c-NKCC1细胞)。转染细胞表现出多达10倍大bumetanide-sensitive Rb(+)相比,控制流入细胞。Balb / c-NKCC1细胞获得典型的表型转换所示:(1)失去接触抑制增长到一个更高的细胞密度表现出的融合性的文化,和细胞病灶的形成;(2)在低血清浓度扩散;和(3)形成的细胞在软琼脂殖民地。控制细胞转染NKCC1基因插入在相反的方向向量保留正常的表型。此外,两个特定的抑制剂钠(+)/ K (+) / Cl(-)转运蛋白活性;单独使用布美他尼和呋喃苯胺酸抑制效率NKCC1转染细胞。 These control experiments indicate that the apparent transformation phenotype acquired by the Balb/c-NKCC1 cells was not merely associated with the process of transfection and selecting for the neomycin-resistant clones, but rather with the overexpression of the Na(+)/K(+)/Cl(-) cotransporter gene. In order to ascertain that the regulated and normal expression of the Na(+)/K(+)/Cl(-) cotransporter control cell proliferation, the effect of bumetanide a specific inhibitor of the cotransporter, was tested on Balb/c 3T3 cell proliferation, induced by fibroblasts growth factor (FGF) and fetal calf serum (FCS). Bumetanide inhibited synchronized Balb/c 3T3 cell exit from the G(0)/G(1) arrest and entering S-phase. The inhibition was reversible, as removal of bumetanide completely released cell proliferation. Taken together, these results propose that the NKCC1 gene is involved in the control of normal cell proliferation, while its overexpression results in apparent cell transformation, in a manner similar to some protooncogenes.

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药物靶点

药物	目标	类	生物	药理作用	行动
布美他尼	溶质载体家庭12成员2	蛋白质	人类	是的	抑制剂	细节