Erythrocyte glutamine depletion, altered redox environment, and pulmonary hypertension in sickle cell disease
Erythrocyte glutamine depletion, altered redox environment, and pulmonary hypertension in sickle cell disease
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DOI：
10.1182/blood-2007-04-081703
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发表时间：
2008-01-01
期刊：
影响因子：
20.3
通讯作者：
Klings, Elizabeth S.
中科院分区：
文献类型：
--
作者：
Morris, Claudia R.;Suh, Jung H.;Klings, Elizabeth S.
红细胞谷胱甘肽耗竭与溶血和氧化应激有关。谷氨酰胺通过保持谷胱甘肽再循环所需的细胞内烟酰胺腺嘌呤二核苷酸磷酸（NADPH）水平发挥额外的抗氧化作用。一氧化氮（NO）生物利用度下降，这发生在增加溶血和氧化应激的设置，有助于肺动脉高压（PH）的发病机制在镰状细胞病（SCD）。我们假设谷胱甘肽和谷氨酰胺代谢的改变在这一过程中发挥作用。本文测定了40例SCD患者和9例健康志愿者血浆和红细胞中总谷胱甘肽（及其前体）和谷氨酰胺的含量。红细胞总谷胱甘肽和谷氨酰胺水平显着低于SCD患者比健康志愿者。谷氨酰胺耗竭与PH独立相关，PH定义为三尖瓣返流射流速度（TRV）至少为2.5 m/s。红细胞谷氨酰胺/谷氨酸比值与TRV呈负相关（r =-0.62，P
Erythrocyte glutathione depletion has been linked to hemolysis and oxidative stress. Glutamine plays an additional antioxidant role through preservation of intracellular nicotinamide adenine dinucleotide phosphate (NADPH) levels, required for glutathione recycling. Decreased nitric oxide (NO) bioavailability, which occurs in the setting of increased hemolysis and oxidative stress, contributes to the pathogenesis of pulmonary hypertension (PH) in sickle cell disease (SCD). We hypothesized that altered glutathione and glutamine metabolism play a role in this process. Total glutathione (and its precursors) and glutamine were assayed in plasma and erythrocytes of 40 SCD patients and 9 healthy volunteers. Erythrocyte total glutathione and glutamine levels were significantly lower in SCD patients than in healthy volunteers. Glutamine depletion was independently associated with PH, defined as a tricuspid regurgitant jet velocity (TRV) of at least 2.5 m/s. The ratio of erythrocyte glutamine:glutamate correlated inversely to TRV (r = -0.62, P