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Measurement of Heme Synthesis Levels in Mammalian Cells
Published on: July 9, 2015
探索共二烯的主要来源:观察红细胞中运输的观察
Karin Brecht1, Pascal Detampel2, Jonny Kinzi1
1Biopharmacy, Department of Pharmaceutical Sciences, University of Basel, Basel, Switzerland.
红细胞通过活性运输从红细胞中释放出基氨酸 (CPs). 多种药物耐药性相关蛋白4 (MRP4),ABCB6和乳腺癌耐药性蛋白 (BCRP) 调解这种流量,影响CP血水平.
科学领域:
- 生物化学 生物化学
- 细胞生物学 细胞生物学
- 药理学 药理学是指药理学的学科.
背景情况:
- 甲酸 (CPs) I和III是血生物合成的副产品,是药物相互作用的潜在生物标志物.
- 红甲状腺细胞产生大多数CP,但它们输出红细胞的机制是未知的.
- 了解CP流动对于解释它们在药物相互作用 (DDI) 预测中的作用至关重要.
研究的目的:
- 调查负责从造血细胞和红状腺细胞中输出基氨酸 (CP) 的排泄载体.
- 为了确定ATP结合盒 (ABC) 载体是否参与红细胞中CP释放.
主要方法:
- 人体网状细胞的蛋白质组分析,以确定潜在的CP流体载体.
- 免疫光显微镜以确认红状腺细胞中的载体表达.
- 在感染过的细胞系和红细胞膜囊泡中进行CP运输测定.
主要成果:
- 蛋白质组数据确定了网状细胞中的多药耐药性相关蛋白 (MRP) 4,ABCB6 和乳腺癌耐药性蛋白 (BCRP).
- 这些ABC载体的表达在CD71阳性网状细胞中得到证实.
- 运输分析表明,MRP4,ABCB6和BCRP调解了Coproporphyrin I和III的外流.
结论:
- 这项研究提供了第一个证据,即ABC载体的活性流动有助于从红细胞释放CP.
- MRP4,ABCB6和BCRP被确定为红细胞CP出口的关键媒介.
- 这些外流载体的功能受损可能会影响血CP水平及其作为生物标志物的有用性.
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