血生长因子维持血小板中的构成性翻译,以调节反应性和血栓潜力
Jeremy G T Wurtzel1, Sophia Lazar1, Shayan Askari1
1Division of Hematology, Department of Medicine, Cardeza Foundation for Hematologic Research, Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, PA.
血生长因子维持血小板转化,对反应性至关重要. 抑制这种翻译会平衡血液静止并防止血栓形成,从而提供新的治疗点.
科学领域:
- 血液学 血液学 血液学
- 分子生物学分子生物学
- 蛋白质稳定性 蛋白质稳定性
背景情况:
- 血小板缺乏核,使其蛋白质稳定机制和功能调节不清楚.
- 据假设,血小板中的构成转化是由血传播的生长因子/激素 (GFHs) 维持的.
研究的目的:
- 调查血GFHs是否保持在循环血小板中的构成性翻译.
- 确定这种翻译在血小板反应性,血液静止和血栓形成中的作用.
主要方法:
- 生物对等非法定氨基酸标记 (BONCAT) 使用质谱学分析血小板转化组.
- 在体外和体内使用循环赫西米德或菌素抑制翻译.
- 在小鼠模型中评估血小板激活 (GpIIb/IIIa,P-selectin),聚合和静血.
主要成果:
- 在人类和小鼠血小板中观察到构成性翻译,这取决于血/GFH暴露.
- 翻译抑制抑制了由血栓素和ADP诱导的血小板激活和聚合.
- 在体内,转化抑制减少了凝块大小,并保护了血管血栓和肺栓塞.
结论:
- 血GFHs驱动血小板中的构成性翻译,调节它们的反应性.
- 这种翻译对于平衡血静和血栓潜力至关重要.
- 针对血小板转化可能为管理血栓性疾病提供新的策略.
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