外源性SPD通过SIRT3调节的线粒体质量控制来抑制trastuzumab介导的心肌细胞灭
Xue Yu1, Yan Yang1, Tianzuo Chen1
1Department of Pathophysiology, School of Basic Medical Sciences, Harbin Medical University, Harbin 150000, China.
International journal of biological sciences
|July 4, 2025
概括
特拉斯图祖马布 (TRZ) 通过损害线粒体引起心脏损伤. 精子胺和SIRT3可以防止这种心脏毒性,为HER2+乳腺癌患者提供潜在的治疗策略.
科学领域:
- 心脏病学 心脏病学
- 在瘤学瘤学.
- 线粒体生物学 线粒体生物学
背景情况:
- 特拉斯图祖马布 (TRZ) 改善了HER2+乳腺癌的存活率,但导致心脏毒性.
- 线粒体质量控制在TRZ诱导的心肌细胞灭中的作用尚未完全理解.
研究的目的:
- 研究TRZ诱导心脏毒性的机制,重点关注线粒体功能障碍和热.
- 评估精氨酸的治疗潜力和SIRT3在缓解TRZ诱导的心脏损伤中的作用.
主要方法:
- 在小鼠模型中评估心脏功能,心肌质炎症和线粒体参数.
- 评估TRZ效应与和没有spermidine补充剂.
- 在野生型和SIRT3淘汰赛小鼠中分析TRZ诱导的心脏损伤.
主要成果:
- TRZ降低了左心室的缩功能,增加了心肌灭症,并诱导了线粒体功能障碍,氧化应激和生物合成的减少.
- 精子胺补充剂通过抑制氧化应激和促进线粒体生物合成来保护心脏功能.
- SIRT3 缺陷加剧了TRZ诱导的心脏损伤和线粒体损伤.
结论:
- 由TRZ诱导的心脏毒性包括线粒体功能障碍和热.
- 精子胺和SIRT3代表了预防TRZ相关心脏损伤的潜在治疗点.
更多相关视频
14:03High-Throughput Cardiotoxicity Screening Using Mature Human Induced Pluripotent Stem Cell-Derived Cardiomyocyte Monolayers
Published on: March 24, 2023
2.0K
07:40Protection of H9c2 Myocardial Cells from Oxidative Stress by Crocetin via PINK1/Parkin Pathway-Mediated Mitophagy
Published on: May 26, 2023
1.3K
相关概念视频
The Extrinsic Apoptotic Pathway
6.6K
The extrinsic apoptotic pathway is initiated when extracellular death-inducing signals, such as specific cytokines, activate the death receptors expressed on the cell surface. The immune cells involved in this pathway are natural killer cells (NK cells) and cytotoxic T-lymphocytes. NK cells are critical in innate immune response, while cytotoxic T-lymphocytes are associated with adaptive immune response. These cells recognize specific receptors expressed on the altered cells and activate...
6.6K
Electron Transport Chain: Complex I and II
15.1K
The mitochondrial electron transport chain (ETC) is the main energy generation system in the eukaryotic cells. However, mitochondria also produce cytotoxic reactive oxygen species (ROS) due to the large electron flow during oxidative phosphorylation. While Complex I is one of the primary sources of superoxide radicals, ROS production by Complex II is uncommon and may only be observed in cancer cells with mutated complexes.
ROS generation is regulated and maintained at moderate levels necessary...
ROS generation is regulated and maintained at moderate levels necessary...
15.1K
