蛋白质稳定和代谢功能障碍在储存诱导的老化红细胞的独特子集中,这些红细胞的清除目标是清除
bioRxiv : the preprint server for biology
|September 24, 2024
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). 这些老化的细胞经历了代谢和蛋白质稳定性改变,标记它们的清除.
科学领域:
- 输血医学 输血医学
- 细胞生物学 细胞生物学
- 老年学是一门学科.
背景情况:
- 红细胞 (RBC) 的冷藏储存对于输血医学至关重要,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尚未完全理解.
研究的目的:
- 描述长期存储的中小企业中的分子和细胞变化.
- 确定导致老化红细胞清除的特定变化.
- 为了研究体外衰老对红细胞代谢和蛋白质稳定性的影响.
主要方法:
- 使用染色协议对长期存储的中小企业 (CFSE高) 和形态正常的红细胞 (CFSE低) 进行分类.
- 进行了代谢学和氧化还原蛋白学,以分析代谢物和蛋白质的变化.
- 评估了红细胞蛋白酶体活性,可变形性,脂素暴露,透脆弱性和内皮细胞粘附性.
- 使用ex vivo人类脏 perfusion 模型评估了 SME 清除.
主要成果:
- 高CFSE的中小企业显示能量,脂质修复和抗氧化剂代谢物的耗尽.
- 在高CFSE的中小企业中观察到不可逆转的蛋白质氧化和蛋白质稳定蛋白的迁移到膜中.
- 高CFSE的中小企业表现出蛋白质酶活性和可变性降低,与增加的脂胺暴露,透脆弱性和内皮细胞粘附性.
- 高CFSE的中小企业在ex vivo脏输液过程中被清除,与CFSE低红细胞不同.
结论:
- 实验室老化选择性地改变了中小企业的新陈代谢和蛋白质稳定.
- 这些分子和细胞变化针对老化的中小企业,以从循环中清除.
- 了解这些变化是改善红细胞储存和输血疗效的关键.
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