ANTISICKLING EFFECTS OF 2,3-DIPHOSPHOGLYCERATE DEPLETION
ANTISICKLING EFFECTS OF 2,3-DIPHOSPHOGLYCERATE DEPLETION
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DOI：
10.1182/blood.v85.11.3289.bloodjournal85113289
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发表时间：
1995-06-01
期刊：
影响因子：
20.3
通讯作者：
KARK, JA
中科院分区：
文献类型：
--
作者：
POILLON, WN;KIM, BC;KARK, JA
镰状红细胞（SS RBC）中2，3-二磷酸甘油酸（2，3-DPG）的升高和伴随的细胞内部酸化通过降低脱氧血红蛋白S的溶解度（c（sat））促进聚合。在乙醇酸-2-磷酸激活双磷酸甘油酸酯的2，3-DPG磷酸酶活性，导致细胞内2，3-DPG的快速损失后，评价2，3-DPG消耗的抗镰状效应。为了确保其在生理介质中的最大降低，使用等渗CO2/碳酸氢盐缓冲盐水（pH 7.0）。K+取代Na+作为主要的细胞外阳离子抑制K：Cl共转运，防止细胞收缩，并允许证明2，3-DPG耗尽的全部抗镰状效应。去除红细胞内2，3-DPG（Δ c（sat）= 1.6 g/dL）对溶解度本身的适度影响通过与影响溶解度和聚合物含量的其他三个细胞变量（细胞内pH值、O-2饱和度和平均细胞血红蛋白浓度）的相互作用而放大为更大的抗镰状效应。这四种抗镰状化作用（三种增溶作用，一种渗透作用）协同作用，使乙醇酸盐处理的SS RBC的聚合物部分减少32%至63%，同时在微循环标称pO（2）（20 mm Hg）下镰状化减少46%至95%。这种程度的镰状化减少应能显著改善镰状细胞病血管闭塞的严重程度。(C)1995年，美国血液学会。
Elevation of 2,3-bisphosphoglycerate (2,3-DPG) in sickle erythrocytes (SS RBCs) and concomitant acidification of the cell interior promote polymerization by decreasing the solubility (c(sat)) of deoxyhemoglobin S. The antisickling effect of 2,3-DPG depletion was evaluated after activation of the 2,3-DPG phosphatase activity of bisphosphoglycerate mutase by glycolate-2-phosphate, leading to rapid loss of intracellular 2,3-DPG. To ensure its maximal reduction in a physiologic medium, isosmotic CO2/bicarbonate-buffered saline, pH 7.0, was used. Substitution of K+ for Na+ as the major extracellular cation suppressed K:Cl cotransport, prevented cell shrinkage, and allowed demonstration of the full antisickling effect of 2,3-DPG depletion. The modest effect on solubility per seof removing intraerythrocytic 2,3-DPG (Delta c(sat) = 1.6 g/dL) was amplified into a much larger antisickling effect by interaction with three other cellular variables affecting solubility and polymer content (intracellular pH, O-2 saturation, and mean cell hemoglobin concentration). Acting in concert, these four antisickling effects (three solubilizing, one osmotic) reduced polymer fraction of glycolate-treated SS RBCs by 32% to 63%, with a concomitant decrease in sickling of 46% to 95% at the nominal pO(2) of the microcirculation (20 mm Hg). A decrement in sickling of this magnitude should significantly ameliorate the vasoocclusive severity of sickle cell disease. (C) 1995 by The American Society of Hematology.