Aminophospholipid translocase and phospholipid scramblase activities in sickle erythrocyte subpopulations
Aminophospholipid translocase and phospholipid scramblase activities in sickle erythrocyte subpopulations
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DOI：
10.1111/j.1365-2141.2009.07760.x
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发表时间：
2009-08-01
影响因子：
6.5
通讯作者：
Franco, Robert S.
中科院分区：
文献类型：
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作者：
Barber, Latorya A.;Palascak, Mary B.;Franco, Robert S.
磷脂酰丝氨酸（PS）外化可能导致镰状细胞病（SCD）的特征，包括血栓形成、内皮粘附和红细胞（RBC）寿命缩短。氨基磷脂移位酶（APLT）将外部化的PS返回到内膜，磷脂乱序酶（PLSCR）平衡磷脂（PL）穿过膜。APLT抑制和PLSCR激活似乎对PS外化很重要。我们检查了成熟镰状红细胞和网织红细胞中APLT、PLSCR和外部PS之间的关系。无外部PS的正常水合镰状红细胞具有活性APLT和非活性PLSCR。PS暴露的镰状红细胞抑制APLT和活性PLSCR。镰状网织红细胞具有独立于外部PS的活性APLT和活性PLSCR。体内脱水的镰状红细胞具有最高比例的PS暴露红细胞，并显著抑制APLT。体外脱水的正常和镰状红细胞APLT中度降低。在体外脱水的红细胞中，再水化导致APLT显著恢复，但在体内脱水的镰状红细胞中则不然。这些发现表明：（i）成熟镰状红细胞中的PS外化取决于APLT和PLSCR活性之间的平衡，（ii）镰状网织红细胞中的PS外化主要取决于PLSCR活化，（iii）体内脱水的镰状红细胞中的APLT抑制是由于脱水本身和其他因素。
Phosphatidylserine (PS) externalization may contribute to Sickle Cell Disease (SCD) characteristics including thrombogenesis, endothelial adhesion and shortened red blood cell (RBC) lifespan. Aminophospholipid translocase (APLT) returns externalized PS to the inner membrane, and phospholipid scramblase (PLSCR) equilibrates phospholipids (PL) across the membrane. APLT inhibition and PLSCR activation appear to be important for PS externalization. We examined relationships between APLT, PLSCR and external PS in mature sickle RBC and reticulocytes. Normally-hydrated sickle RBC without external PS had active APLT and inactive PLSCR. PS-exposing sickle RBC had inhibited APLT and active PLSCR. Sickle reticulocytes had active APLT and active PLSCR independent of external PS. Sickle RBC dehydrated in vivo had the highest proportion of PS-exposing RBC and markedly inhibited APLT. Normal and sickle RBC dehydrated in vitro had moderately decreased APLT. Rehydration resulted in significant recovery of APLT in RBC previously dehydrated in vitro, but not in sickle RBC dehydrated in vivo. These findings indicate that (i) PS externalization in mature sickle RBC depends on the balance between APLT and PLSCR activities, (ii) PS externalization in sickle reticulocytes depends primarily on PLSCR activation and (iii) APLT inhibition in sickle RBC dehydrated in vivo is due to dehydration itself and other factors.