purinosomes 和 lysosomes 相互作用,以维持纯素池
Yubing Liu1, Vidhi Pareek2, Dipankar Bhowmik1
1Department of Chemistry, Eberly College of Science, The Pennsylvania State University, University Park, PA 16802, United States.
概括
溶解体从消化的DNA/RNA中回收精氨酸,补偿缺陷. 这种 lysosome-mediated purin 挽救途径与 de novo purin 生物合成 (DNPB) 一起工作,以维持癌细胞中必需的 purin 池.
科学领域:
- 细胞生物学 细胞生物学
- 代谢生物化学 代谢生物化学
- 癌症研究 癌症研究
背景情况:
- purin 是重要的 DNA / RNA 构建块,具有已确定的救援和 de novo 合成 (DNPB) 的途径.
- 核酸的溶酶体消化和随后的纯素再吸收的作用在很大程度上仍然没有被描述.
- 了解纯素代谢对于癌症治疗至关重要,因为癌细胞对纯素有很高的需求.
研究的目的:
- 在人类癌症细胞系中研究 lysosome-mediated purin 循环.
- 探索 lysosomal purin 救援和 DNPB.之间的协调.
- 为了确定 lysosomal 途径对维持细胞纯素池的贡献.
主要方法:
- 使用了细胞内稳定同位素合并试验.
- 采用定量代谢学来进行综合分析.
- 开发并使用细胞内RNA-FRET基分析法来可视化RNA消化.
主要成果:
- 发现细胞对外部纯素的吸收和内部纯素的产生是相当的.
- 甲托雷克萨特 (MTX) 和洛美特雷克索尔 (LTX) 治疗诱导了溶酶体生物发生,以应对纯素缺乏.
- 降低了 lysosomal RNase 活性 (通过 RNAseT2 淘汰) 导致了 RNA 积累和补偿 DNPB 上调.
结论:
- 溶解体在通过核酸消化和再吸收的纯素循环中发挥着重要作用.
- 在 purin 缺乏期间, lysosome-mediated purin 挽救被上调,与 DNPB 协调.
- 这一途径对于维持人类癌细胞中总池的维持至关重要.
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