PubMed日本語 - 鎌状赤血球ヘモグロビンは、赤血球O2含有量、解糖と総抗酸化能の間で正常な結合を妨げる。―QLifePro医療翻訳医療翻訳 QLifePro



Sickle hemoglobin disturbs normal coupling among erythrocyte O2 content, glycolysis, and antioxidant capacity.

Published date 2013 Jan 7

Sickle hemoglobin disturbs normal coupling among erythrocyte O2 content, glycolysis, and antioxidant capacity.


Published date



Stephen C Rogers, Jerlinda G C Ross, Andre d'Avignon, Lindsey B Gibbons, Vered Gazit, Mojibade N Hassan, Dylan McLaughlin, Sherraine Griffin, Tara Neumayr, Malcolm Debaun, Michael R DeBaun, Allan Doctor


Division of Critical Care Medicine, Department of Pediatrics, Washington University School of Medicine, 1 Children's Pl, St Louis, MO 63110, USA.


Energy metabolism in RBCs is characterized by O2-responsive variations in flux through the Embden Meyerhof pathway (EMP) or the hexose monophosphate pathway (HMP). Therefore, the generation of ATP, NADH, and 2,3-DPG (EMP) or NADPH (HMP) shift with RBC O2 content because of competition between deoxyhemoglobin and key EMP enzymes for binding to the cytoplasmic domain of the Band 3 membrane protein (cdB3). Enzyme inactivation by cdB3 sequestration in oxygenated RBCs favors HMP flux and NADPH generation (maximizing glutathione-based antioxidant systems). We tested the hypothesis that sickle hemoglobin disrupts cdB3-based regulatory protein complex assembly, creating vulnerability to oxidative stress. In RBCs from patients with sickle cell anemia, we demonstrate in the present study constrained HMP flux, NADPH, and glutathione recycling and reduced resilience to oxidative stress manifested by membrane protein oxidation and membrane fragility. Using a novel, inverted membrane-on-bead model, we illustrate abnormal (O2-dependent) association of sickle hemoglobin to RBC membrane that interferes with sequestration/inactivation of the EMP enzyme GAPDH. This finding was confirmed by immunofluorescent imaging during RBC O2 loading/unloading. Moreover, selective inhibition of inappropriately dispersed GAPDH rescues antioxidant capacity. Such disturbance of cdB3-based linkage between O2 gradients and RBC metabolism suggests a novel mechanism by which hypoxia may influence the sickle cell anemia phenotype.


従って、ATPの世代、NADH、そして、2,3-DPG(EMP)または3つの膜蛋白質(cdB3)を帯の細胞質領域に結合するためのデオキシヘモグロビンとキーEMP酵素間の競争のため、RBC O2含有量によるNADPH(HMP)推移。
小説(逆位のビードの膜モデル)を使用する、我々はこの発見がそうであったEMP酵素GAPDH.の腐骨形成/不活性化を邪魔するRBC膜に鎌状赤血球ヘモグロビンの異常な(O2依存的な)関連を例示するRBC O2積載/負荷軽減の間の免疫蛍光画像診断によって確認する。

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