新型血红蛋白变构调节剂对红细胞氧亲和力的调节作用与波尔效应相加。

Modulation of red blood cell oxygen affinity with a novel allosteric modifier of hemoglobin is additive to the Bohr effect.

机构信息

Duke University School of Medicine, Durham, NC, United States of America.

出版信息

Blood Cells Mol Dis. 2021 Mar;87:102520. doi: 10.1016/j.bcmd.2020.102520. Epub 2020 Nov 19.

DOI:10.1016/j.bcmd.2020.102520

PMID:33242840

Abstract

PURPOSE

The Bohr effect describes hemoglobin's affinity for oxygen dependent on solution pH. Within pH range 6.0-8.5, hemoglobin's oxygen affinity decreases with decreasing pH. This results in increased oxygen delivery to metabolically active, acidic tissues and improved oxygen uptake in basic regions including lung tissue. Myo-Inositol tripyrophosphate (ITPP) translocates the erythrocyte membrane and allosterically modifies hemoglobin (Hb). We tested the hypothesis that ITPP does not abrogate the Bohr effect.

METHODS

Experiments were conducted to determine the effect of increasing concentrations of ITPP on P50 with varying pH. We incubated 10 mL red blood cells at 37 °C for 1 h with ITPP concentrations from 0 to 240 mM. The Clark oxygen electrode (Hemox-Analyzer; TCS Scientific, New Hope, PA) determined oxygen affinity of each sample, in triplicate, using buffers pH 6.8, 7.4, and 7.6. A mixed linear regression model with fixed effects for ITPP concentration and pH was used.

RESULTS

Increasing ITPP concentration and decreasing pH increased P50 (p < 0.0001 for ITPP concentration, p < 0.0001 for pH). ITPP modulated increased P50 in normal pH (7.4) and acidic condition pH (6.8); with no effect at alkaline pH (7.6).

CONCLUSION

The Bohr effect is conserved, with ITPP augmenting the decreased oxygen affinity seen with tissue acidosis, while not affecting oxygen affinity in conditions similar to a pulmonary microenvironment.

摘要

目的

波尔效应描述了血红蛋白对氧的亲和力取决于溶液的 pH 值。在 pH 值 6.0-8.5 的范围内，血红蛋白的氧亲和力随 pH 值的降低而降低。这导致代谢活跃的酸性组织的氧输送增加，以及包括肺组织在内的碱性区域的氧摄取增加。肌醇三磷酸（ITPP）可转运红细胞膜并变构修饰血红蛋白（Hb）。我们检验了这样一个假设，即 ITPP 不会消除波尔效应。

方法

进行了实验以确定增加 ITPP 浓度对 P50 的影响，同时 pH 值也在变化。我们将 10 mL 红细胞在 37°C 下孵育 1 小时，ITPP 浓度从 0 到 240 mM。Clark 氧电极（Hemox-Analyzer；TCS Scientific，New Hope，PA）使用 pH 值为 6.8、7.4 和 7.6 的缓冲液，分别重复三次测定每个样本的氧亲和力。采用固定效应为 ITPP 浓度和 pH 值的混合线性回归模型。