Sulphydryl modifications alter scramblase activity in murine sickle cell disease
Sulphydryl modifications alter scramblase activity in murine sickle cell disease
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DOI：
10.1111/j.1365-2141.2006.06045.x
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发表时间：
2006-05-01
影响因子：
6.5
通讯作者：
Kuypers, FA
中科院分区：
文献类型：
--
作者：
de Jong, K;Kuypers, FA
增加的氧化应激已被认为在镰状细胞患者红细胞中磷脂酰丝氨酸（PS）外化过程中发挥作用。巯基修饰可以抑制atp驱动的从外到内单层（翻转酶）的易位。本研究表明磷脂搅合对蛋白质巯基修饰也很敏感。用n -乙基马来酰亚胺处理会增加PS暴露，降低置乱所需的Ca++。相比之下，吡啶二硫乙胺处理抑制PS暴露。镰状细胞病小鼠模型的红细胞对这两种试剂的反应降低，提示先前对参与磷脂混乱的蛋白质进行巯基修饰。我们得出的结论是，在镰状细胞病中，巯基修饰的超转录酶和翻转酶是ps暴露细胞增强形成的基础。
Increased oxidant stress has been suggested to play a role in the process of phosphatidylserine (PS) externalisation in the red blood cells of sickle cell patients. Inhibition of the ATP-driven translocation from outer to inner monolayer (flippase) by sulphydryl modification has been established. The present study showed that phospholipid scrambling was also sensitive to protein sulphydryl modification. Treatment with N-ethylmaleimide lead to enhanced PS exposure and a lower Ca++ requirement for scrambling. In contrast, pyridyldithioethylamine treatment inhibited PS exposure. Red blood cells from a murine model for sickle cell disease exhibited a reduced response to both reagents, suggestive of previous sulphydryl modifications to the protein(s) involved in phospholipid scrambling. We conclude that sulphydryl modifications to both scramblase and flippase underlie the enhanced formation of PS-exposing cells in sickle cell disease.