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Proteasome is a carrier to translocate doxorubicin from cytoplasm into nucleus.

机译:蛋白酶体是将阿霉素从细胞质转运到细胞核的载体。

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When an effective concentration of doxorubicin (DXR) was added into L1210 of a mouse leukemia cell line, DXR was rapidly distributed much more in the nuclei than in the other organelle within a few minutes. A [14C]DXR-binding fraction was obtained from the cytosol prepared from L1210 cells. The fraction was adsorbed to hydroxylapatite matrix and eluted from the matrix by 50-150 mM potassium phosphate buffer. The fraction showed high DXR-binding and Suc-Leu-Leu-Val-Tyr-MCA-degrading activity. The binding of [14C]DXR was inhibited by unlabeled DXR. Gel chromatography of the fraction with Sephacryl S-300 separated two fractions of high molecular weight (Peak I, approx. 750 kDa) and low molecular weight (Peak II). Peak I showed proteolytic activity. [14C]DXR-binding Peak I had much higher affinity to DNA-cellulose than [14C]DXR-binding Peak II. [14C]DXR-Peak I complex also was retained into the nuclei isolated from L1210 cells, temperature-dependently. These results suggest that a specific carrier to translocate DXR from cytoplasm into nucleus exists in L1210 cell and the carrier is proteasome.
机译:当将有效浓度的阿霉素(DXR)添加到小鼠白血病细胞系的L1210中时,在几分钟内DXR在细胞核中的分布远快于其他细胞器。从由L1210细胞制备的胞质溶胶中获得[14C] DXR结合级分。将级分吸附到羟基磷灰石基质上,并用50-150 mM磷酸钾缓冲液从基质上洗脱。该级分显示出高的DXR结合和Suc-Leu-Leu-Val-Tyr-MCA降解活性。 [14C] DXR的结合被未标记的DXR抑制。用Sephacryl S-300进行级分的凝胶色谱分离,分离出两个高分子量(峰I,约750 kDa)和低分子量(峰II)的馏分。峰I显示出蛋白水解活性。 [14C] DXR结合峰I对DNA纤维素的亲和力比[14C] DXR结合峰II高。 [14C] DXR-Peak I复合物也保留在从L1210细胞分离的细胞核中,并具有温度依赖性。这些结果表明在L1210细胞中存在将DXR从细胞质转位至细胞核的特异性载体,并且该载体是蛋白酶体。

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