Glutathione protects chemokine-scavenging and antioxidative defense functions in human RBCs
Glutathione protects chemokine-scavenging and antioxidative defense functions in human RBCs
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DOI：
10.1152/ajpcell.2001.280.4.c867
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发表时间：
2001-04-01
影响因子：
5.5
通讯作者：
Jacobsen, DW
中科院分区：
文献类型：
--
作者：
Dumaswala, UJ;Zhuo, L;Jacobsen, DW
已知体内或体外的氧化应激可诱导人红细胞（rbc）的氧化变化。我们的目的是研究增加红细胞谷胱甘肽（GSH）合成对1)退行性蛋白损失和2)红细胞趋化因子和自由基清除功能的影响，通过使用储存的红细胞作为模型。将包装好的红细胞在Adsol或实验添加剂溶液（Adsol中添加谷氨酰胺、甘氨酸和n -乙酰- l-半胱氨酸）中保存84天，温度为1-6℃。在常规添加剂中添加谷胱甘肽前体氨基酸可以改善红细胞谷胱甘肽的合成和维持。红细胞γ -谷氨酰半胱氨酸连接酶活性的升高与GSH含量成正比，与细胞外同型半胱氨酸浓度、高铁血红蛋白形成、红细胞蛋白3、4.1、4.2、甘油醛-3-磷酸脱氢酶和Duffy抗原的损失成反比（P < 0.01）。Duffy抗原丢失的减少与趋化因子RANTES（受激活、正常t细胞表达和分泌调节）浓度的降低密切相关。我们得出结论，氧化应激红细胞中GSH和蛋白质的损失会损害红细胞的清除功能。上调GSH合成可保护红细胞清除（自由基和趋化因子）功能。这些结果不仅对输血环境有影响，而且对糖尿病和镰状细胞性贫血等疾病也有影响，其中红细胞受到慢性/急性氧化应激。
Oxidant stress, in vivo or in vitro, is known to induce oxidative changes in human red blood cells (RBCs). Our objective was to examine the effect of augmenting RBC glutathione (GSH) synthesis on 1) degenerative protein loss and 2) RBC chemokine- and free radical-scavenging functions in the oxidatively stressed human RBCs by using banked RBCs as a model. Packed RBCs were stored up to 84 days at 1-6 degreesC in Adsol or in the experimental additive solution (Adsol fortified with glutamine, glycine, and N-acetyl-L-cysteine). Supplementing the conventional additive with GSH precursor amino acids improved RBC GSH synthesis and maintenance. The rise in RBC gamma -glutamylcysteine ligase activity was directly proportional to the GSH content and inversely proportional to extracellular homocysteine concentration, methemoglobin formation, and losses of the RBC proteins band 3, band 4.1, band 4.2, glyceraldehyde-3-phosphate dehydrogenase, and Duffy antigen (P < 0.01). Reduced loss of Duffy antigen correlated well with a decrease in chemokine RANTES (regulated upon activation, normal T-cell expressed, and secreted) concentration. We conclude that the concomitant loss of GSH and proteins in oxidatively stressed RBCs can compromise RBC scavenging function. Upregulating GSH synthesis can protect RBC scavenging (free radical and chemokine) function. These results have implications not only in a transfusion setting but also in conditions like diabetes and sickle cell anemia, in which RBCs are subjected to chronic/acute oxidant stresses.