Red blood cells (RBCs) are susceptible to sustained free radical damage during circulation, while the changes of antioxidant capacity and regulatory mechanism of RBCs under different oxygen gradients remain unclear. Here, we investigated the changes of oxidative damage and antioxidant capacity of RBCs in different oxygen gradients and identified the underlying mechanisms using an in vitro model of the hypoxanthine/xanthine oxidase (HX/XO) system. In the present study, we reported that the hypoxic RBCs showed much higher oxidative stress injury and lower antioxidant capacity compared with normoxic RBCs. In addition, we found that the disturbance of the recycling process, but not de novo synthesis of glutathione (GSH), accounted for the significantly decreased antioxidant capacity of hypoxic RBCs compared to normoxic RBCs. We further elucidated the underlying molecular mechanism by which oxidative phosphorylation of Band 3 blocked the hexose monophosphate pathway (HMP) and decreased NADPH production aggravating the dysfunction of GSH synthesis in hypoxic RBCs under oxidative conditions.

中文翻译：

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谷胱甘肽的下调回收过程，但不是从头合成，限制了缺氧条件下红细胞的抗氧化能力。

红细胞（RBC）在循环过程中容易受到自由基的破坏，而在不同的氧气梯度下红细胞的抗氧化能力和调节机制的变化仍不清楚。在这里，我们研究了在不同的氧气梯度下红细胞的氧化损伤和抗氧化能力的变化，并使用次黄嘌呤/黄嘌呤氧化酶（HX / XO）系统的体外模型确定了潜在的机制。在本研究中，我们报道了与常氧RBC相比，低氧RBC显示出更高的氧化应激损伤和更低的抗氧化能力。此外，我们发现，对再循环过程的干扰，而不是谷胱甘肽（GSH）的从头合成，是造成缺氧RBC与抗氧RBC相比抗氧化能力显着降低的原因。