脂肪细胞成熟会影响罗素的分泌和代谢
Zeyang Li1, Rachael Ngu1, Aditya Anil Naik1
1Alfred Mann School of Pharmacy and Pharmaceutical Sciences, University of Southern California, Los Angeles, California, USA.
European journal of clinical investigation
|September 10, 2024
概括
肥胖增加了儿童白血病的化疗耐药性,因为它增强了脂肪细胞中dorubicin (DNR) 的代谢. 这通过增加特定酶的表达而发生,这表明肥胖可能是改善治疗结果的目标.
科学领域:
- 生物化学 生物化学
- 在瘤学瘤学.
- 细胞生物学 细胞生物学
背景情况:
- 儿童急性淋巴细胞白血病 (ALL) 可以通过化疗治疗.
- 肥胖与ALL患者的抗化学药性增加和生存率降低有关.
- 肥胖驱动的化学抵抗的分子基础仍然不清楚.
研究的目的:
- 调查脂肪细胞成熟如何影响化疗药物达诺鲁比 (DNR) 的封存和代谢.
- 为了确定参与脂肪细胞内DNR代谢的特定酶.
主要方法:
- 使用了人类前脂肪细胞和脂肪细胞细胞系.
- 有针对性的LC-MS/MS测定测量了DNR封存和代谢.
- 评估了阿尔多基因减少酶 (AKR) 和碳基因减少酶 (CBR) 的表达.
- 用重组酶和特定抑制剂来识别关键的代谢异型.
主要成果:
- 脂肪细胞成熟显著上调AKR和CBR酶表达 (4至60倍).
- 在脂肪细胞中,与前脂肪细胞相比,DNR封存和代谢增加了大约30%.
- AKR1C3和CBR1被确定为负责DNR生物转化的主要异型.
结论:
- 脂肪组织可以通过高调节的AKR1C3和CBR1酶隔离和排毒DNR,特别是在肥胖症中.
- 这种机制提供了一部分解释肥胖的ALL患者中化学抵抗的DNR.
- 针对肥胖症可能是一个可行的策略,以减少ALL中DNR化学抵抗.
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