Deferoxamine deconditioning increases neuronal vulnerability to hemoglobin.
Deferoxamine deconditioning increases neuronal vulnerability to hemoglobin.
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DOI：
10.1016/j.yexcr.2020.111926
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发表时间：
2020-02
影响因子：
3.7
通讯作者：
Denggao Peng;C. Chen;Deepa Ruhela;Yang Li;R. Regan
中科院分区：
文献类型：
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作者：
Denggao Peng;C. Chen;Deepa Ruhela;Yang Li;R. Regan
同时使用去铁胺（DFO）治疗可保护神经细胞免受铁和血红素介导的氧化损伤，但也会破坏细胞对可能具有保护作用的铁负荷的反应。我们假设DFO治疗和停药会增加神经元对血红蛋白的脆弱性。与对照载体预处理的培养物相比，用DFO预处理后洗脱，在随后的血红蛋白暴露后增加3-4倍的神经元损失。这与血红蛋白诱导铁蛋白减少有关;催化血红素释放铁的血红素加氧酶-1的表达没有改变。在整个实验过程中，外源性脱铁铁蛋白或持续DFO或抗氧化剂可防止神经元丢失增加。血红蛋白处理后的细胞非血红素铁水平在DFO预处理和对照培养物中相似。这些结果表明，DFO decoditions神经元，随后增加他们的脆弱性血红素介导的损伤。其在CNS出血后的净效应可能高度依赖于其给药的时间和持续时间。在血红素或铁水平保持升高的情况下停用DFO可能是有害的，并且可能抵消先前伴随治疗的任何益处。
Concomitant treatment with deferoxamine (DFO) protects neural cells from iron and heme-mediated oxidative injury, but also disrupts cell responses to iron loading that may be protective. We hypothesized that DFO treatment and withdrawal would subsequently increase neuronal vulnerability to hemoglobin. Pretreatment with DFO followed by its washout increased neuronal loss after subsequent hemoglobin exposure by 3-4-fold compared with control vehicle-pretreated cultures. This was associated with reduced ferritin induction by hemoglobin; expression of heme oxygenase-1, which catalyzes iron release from heme, was not altered. Increased neuronal loss was prevented by exogenous apoferritin or by continuing DFO or antioxidants throughout the experimental course. Cell nonheme iron levels after hemoglobin treatment were similar in DFO-pretreated and control cultures. These results indicate that DFO deconditions neurons and subsequently increases their vulnerability to heme-mediated injury. Its net effect after CNS hemorrhage may be highly dependent on the timing and duration of its administration. Withdrawal of DFO while heme or iron levels remain elevated may be deleterious, and may negate any benefit of prior concomitant therapy.