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衰老小鼠肺树突状细胞中多药耐药蛋白 1 和多药耐药相关蛋白 1 的表达和功能。

Expression and function of multidrug resistance protein 1 and multidrug resistance-associated protein 1 in lung dendritic cells from aging mice.

机构信息

Second Division, Department of Internal Medicine, Hamamatsu University School of Medicine, Hamamatsu, Japan.

出版信息

J Gerontol A Biol Sci Med Sci. 2012 Oct;67(10):1049-55. doi: 10.1093/gerona/gls069. Epub 2012 Mar 26.

Abstract

Multidrug resistance protein 1 and multidrug resistance-associated protein 1 are transporters that efflux diverse xenobiotics from cells. We investigated changes in the expression and activity of multidrug resistance protein 1 and multidrug resistance-associated protein 1 in highly purified lung dendritic cells (LDCs) during aging using magnetic and flow cytometric cell sorting. Multidrug resistance protein 1 blockade by the specific inhibitor reduced the percentage of rhodamine 123(low) cells in LDCs from aged mice (54.8% ± 2.6% to 13.2% ± 2.5%, p < .01). The difference in the proportions of rhodamine 123(low) cells in aged LDCs was more apparent than that in LDCs from young mice (p < .05). The multidrug resistance-associated protein 1-specific inhibitor reduced the percentage of Fluo-3(low) cells in aged LDCs (60.8% ± 5.3% to 25.8% ± 7.5%, p < .01). The difference in the proportions of Fluo-3(low) cells in aged LDCs was smaller than that in young LDCs (p < .05). These data showed that LDCs from aged mice exhibited multidrug resistance protein 1- and multidrug resistance-associated protein 1-mediated efflux and that the age-associated changes differed according to transporters.

摘要

多药耐药蛋白 1 和多药耐药相关蛋白 1 是将多种外源性物质从细胞中排出的转运蛋白。我们使用磁性和流式细胞术细胞分选研究了在衰老过程中高度纯化的肺树突状细胞(LDCs)中多药耐药蛋白 1 和多药耐药相关蛋白 1 的表达和活性变化。多药耐药蛋白 1 的特异性抑制剂阻断降低了来自老年小鼠的 LDCs 中罗丹明 123(低)细胞的比例(54.8%±2.6%至 13.2%±2.5%,p<.01)。与年轻小鼠的 LDCs 相比,老年 LDCs 中罗丹明 123(低)细胞的比例差异更为明显(p<.05)。多药耐药相关蛋白 1 的特异性抑制剂降低了来自老年 LDCs 的 Fluo-3(低)细胞的比例(60.8%±5.3%至 25.8%±7.5%,p<.01)。老年 LDCs 中 Fluo-3(低)细胞的比例差异小于年轻 LDCs(p<.05)。这些数据表明,来自老年小鼠的 LDCs 表现出多药耐药蛋白 1 和多药耐药相关蛋白 1 介导的外排作用,并且与年龄相关的变化根据转运蛋白而有所不同。

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