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首页> 外文期刊>Neurochemistry International: The International Journal for the Rapid Publication of Critical Reviews, Preliminary and Original Research Communications in Neurochemistry >Hemopexin decreases hemin accumulation and catabolism by neural cells
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Hemopexin decreases hemin accumulation and catabolism by neural cells

机译：血色素减少神经细胞对血红素的积累和分解代谢

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摘要

Hemopexin is a serum, CSF, and neuronal protein that is protective after experimental stroke. Its efficacy in the latter has been linked to increased expression and activity of heme oxygenase (HO)-1, suggesting that it facilitates heme degradation and subsequent release of cytoprotective biliverdin and carbon monoxide. In this study, the effect of hemopexin on the rate of hemin breakdown by CNS cells was investigated in established in vitro models. Equimolar hemopexin decreased hemin breakdown, as assessed by gas chromatography, by 60-75% in primary cultures of murine neurons and glia. Extracellular hemopexin reduced cell accumulation of 55Fe-hemin by over 90%, while increasing hemin export or extraction from membranes by fourfold. This was associated with significant reduction in HO-1 expression and neuroprotection. In a cell-free system, hemin breakdown by recombinant HO-1 was reduced over 80% by hemopexin; in contrast, albumin and two other heme-binding proteins had no effect. Although hemopexin was detected on immunoblots of cortical lysates from adult mice, hemopexin knockout per se did not alter HO activity in cortical cells treated with hemin. These results demonstrate that hemopexin decreases the accumulation and catabolism of exogenous hemin by neural cells. Its beneficial effect in stroke models is unlikely to be mediated by increased production of cytoprotective heme breakdown products.
机译：血凝素是实验性中风后具有保护作用的血清，脑脊液和神经元蛋白。它在后者中的功效与血红素加氧酶（HO）-1的表达和活性增加有关，表明它促进了血红素的降解以及随后释放的细胞保护性胆绿素和一氧化碳。在这项研究中，在建立的体外模型中研究了血红素对中枢神经系统细胞的血红素分解率的影响。通过气相色谱法评估，等摩尔的血红蛋白减少了鼠神经元和神经胶质原代培养物中的血红素分解，降低了60-75％。细胞外溶血素减少了55Fe-hemin的细胞积累90％以上，同时使hemin的出口或从膜中的提取增加了四倍。这与HO-1表达和神经保护的显着降低有关。在无细胞系统中，重组人HO-1对血红素的分解作用被血红素减少了80％以上。相反，白蛋白和其他两种血红素结合蛋白没有作用。尽管在成年小鼠的皮质裂解物的免疫印迹中检测到了血红蛋白，但血红蛋白的敲除本身并未改变用血红素处理过的皮质细胞中的HO活性。这些结果表明，血红蛋白减少了神经细胞对外源性血红素的积累和分解代谢。它在中风模型中的有益作用不太可能由细胞保护性血红素分解产物的产生来介导。

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