转录组学与蛋白质组学相结合,揭示了 osimertinib 诱导的心肌线粒体功能障碍
Haichao Yang1, Suhua Qiu2, Tiezhu Yao1
1Department of Cardiology, The Fourth Hospital of Hebei Medical University, Shijiazhuang 050010, China.
Toxicology letters
|May 11, 2024
概括
奥西默提尼布通过破坏线粒体功能和减少ATP生产而导致心脏损伤. 这项研究揭示了这种心脏毒性背后的机制,为接受治疗的癌症患者提供了洞察力.
科学领域:
- 心脏病学 心脏病学
- 分子生物学分子生物学
- 在瘤学瘤学.
背景情况:
- 奥西默提尼布是一种表皮生长因子受体氨酸激酶抑制剂 (EGFR-TKI),在癌症治疗中至关重要.
- 心脏毒性是已知的 osimertinib 的副作用,但其潜在机制仍然不清楚.
研究的目的:
- 为了阐明 osimertinib 诱导心脏毒性的分子机制.
- 调查奥西默提尼布对心脏线粒体功能和能量生产的影响.
主要方法:
- 向小鼠和新生小鼠心室肌细胞 (NRVMs) 给予奥西默蒂尼布.
- 利用4D无标签蛋白质组学和RNA测序来进行全面的分子分析.
- 进行了基因和基因组京都百科全书 (KEGG) 途径分析.
主要成果:
- 奥西默提尼布在小鼠中诱导了显著的心脏结构和功能损伤,损伤生物标志物增加.
- 用osimertinib治疗的NRVM显示在氧化酸化 (OXPHOs) 中差异表达的基因和蛋白质的丰富.
- 奥西默提尼布破坏了ATP合成酶 (复合V) 功能,导致腺三酸盐 (ATP) 水平降低和线粒体功能受损.
结论:
- 奥西默提尼布诱导的心脏毒性是由线粒体功能障碍介导的.
- 破坏OXPHOs和随后减少ATP生产是导致心脏损伤的关键机制.
- 这些发现提供了对 osimertinib 心脏毒性的机制性理解,这对于治疗癌症患者至关重要.
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