蛋白质稳定和代谢功能障碍是储存诱导的老化红细胞的一个子集的特征,这些红细胞的目标是输血后清除
Sandy Peltier1,2, Mickaël Marin1, Monika Dzieciatkowska3
1Université Paris Cité, INSERM, BIGR, Paris, France.
The Journal of clinical investigation
|March 11, 2025
概括
储存红细胞 (RBC) 中的细胞衰老导致储存诱导的微红细胞 (SMEs). 这些老化的红细胞表现出代谢,蛋白质和功能变化,导致它们在输血后的清除.
科学领域:
- 血液学 血液学 血液学
- 细胞生物学 细胞生物学
- 生物化学 生物化学
背景情况:
- 冰箱储存对于红细胞 (RBC) 输血药物至关重要,但会诱导细胞衰老.
- 储存诱导的微红细胞 (SMEs) 是衰老的红细胞,在储存期间积累,并在输血后被清除.
- 触发中小企业清算的分子机制仍未确定.
研究的目的:
- 确定在体外老化的红细胞中导致其清除的分子和细胞变化.
- 描述储存诱导的微红细胞 (SMEs),并将其与形态正常的红细胞进行比较.
主要方法:
- 使用染色协议从形态正常的红细胞 (CFSElo) 排序长期存储的老红细胞 (CFSEhi).
- 进行了代谢学,氧化还原蛋白学和蛋白学分析.
- 评估了红细胞蛋白酶体活性,可变形性,脂素暴露,透性脆弱性和内皮细胞粘附性.
- 使用ex vivo人类脏输液评估的红细胞清除.
主要成果:
- CFSEhi红细胞显示能量耗尽,脂质修复和抗氧化剂代谢产物.
- 在CFSEhi红细胞中观察到不可逆转的蛋白质氧化和蛋白质稳定蛋白向膜的转移.
- CFSEhi红细胞表现出蛋白质酶活性和可变性降低,酸素暴露增加,透脆弱性和内皮细胞粘附性.
- 与CFSElo红细胞不同的是,CFSEhi红细胞在ex vivo perfusion中被清除.
结论:
- 储存诱导的微红细胞 (SMEs) 是形态和代谢改变的衰老的红细胞.
- 这些老化的红细胞具有不可逆转的氧化蛋白和改变的蛋白质稳定性,导致功能下降.
- 由于这些因体外衰老引起的变化,中小企业被选择性地从流通中清除.
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