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Deferoxamine deconditioning increases neuronal vulnerability to hemoglobin.
Experimental Cell Research ( IF 3.7 ) Pub Date : 2020-02-26 , DOI: 10.1016/j.yexcr.2020.111926
Denggao Peng 1 , Cindy Acon Chen 1 , Deepa Ruhela 1 , Yang Li 1 , Raymond F Regan 1
Affiliation  

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.

中文翻译:

去铁胺失调会增加神经元对血红蛋白的脆弱性。

伴随去铁胺(DFO)的治疗可保护神经细胞免受铁和血红素介导的氧化损伤,但也会破坏细胞对铁负载的反应,这可能是保护性的。我们假设DFO治疗和戒断会随后增加神经元对血红蛋白的脆弱性。与对照媒介物预处理的培养物相比,DFO预处理及其后的冲蚀作用使随后的血红蛋白暴露后神经元损失增加了3-4-倍。这与血红蛋白对铁蛋白的诱导减少有关。血红素加氧酶-1的表达,催化铁从血红素的释放,没有改变。在整个实验过程中,外源性脱铁铁蛋白或持续的DFO或抗氧化剂可防止神经元增加。在DFO预处理和对照培养物中,血红蛋白处理后的细胞非血红素铁水平相似。这些结果表明,DFO使神经元失调,从而增加了它们对血红素介导的损伤的脆弱性。中枢神经系统出血后其净效应可能高度取决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同时撤出DFO可能有害,并且可能抵消先前伴随治疗的任何益处。
更新日期:2020-02-26
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