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白细胞介素-1β通过调节铜蓝蛋白和铁转运蛋白-1的合成上调大鼠C6胶质瘤细胞中的铁外流。

Interleukin-1beta up-regulates iron efflux in rat C6 glioma cells through modulation of ceruloplasmin and ferroportin-1 synthesis.

作者信息

di Patti Maria Carmela Bonaccorsi, Persichini Tiziana, Mazzone Valeria, Polticelli Fabio, Colasanti Marco, Musci Giovanni

机构信息

Department of Biochemical Sciences, University "La Sapienza", p.le Aldo Moro 5, I-00185 Rome, Italy.

出版信息

Neurosci Lett. 2004 Jun 10;363(2):182-6. doi: 10.1016/j.neulet.2004.04.005.

Abstract

A number of pathologies, including neurodegeneration and inflammation, have been associated with iron dysmetabolism in the brain. Hence, systems involved in iron homeostasis at the cellular level have aroused considerable interest in recent years. The iron exporter ferroportin-1 (FP) and the multicopper oxidase ceruloplasmin (CP) are essential for iron efflux from cells. By using RT-PCR, we demonstrate that FP and CP gene expression is up-regulated by treatment with the pro-inflammatory cytokine IL-1beta in rat C6 cells, taken as a glial cellular model. Following stimulation with IL-1beta, a higher expression level of CP and FP was also confirmed by Western blotting. Moreover, IL-1beta has been found to increase iron efflux from C6 cells, suggesting that both proteins may play a crucial role in iron homeostasis in pathological brain conditions, such as inflammatory and/or neurodegenerative diseases.

摘要

包括神经退行性变和炎症在内的多种病理状况已与大脑中铁代谢异常相关。因此,近年来细胞水平上参与铁稳态的系统引起了人们极大的兴趣。铁输出蛋白铁转运蛋白1(FP)和多铜氧化酶铜蓝蛋白(CP)对于铁从细胞中流出至关重要。通过逆转录聚合酶链反应(RT-PCR),我们证明在作为神经胶质细胞模型的大鼠C6细胞中,促炎细胞因子白细胞介素-1β(IL-1β)处理可上调FP和CP基因表达。在用IL-1β刺激后,蛋白质印迹法也证实了CP和FP的表达水平更高。此外,已发现IL-1β可增加C6细胞的铁流出,这表明这两种蛋白质可能在诸如炎症和/或神经退行性疾病等病理性脑疾病的铁稳态中起关键作用。

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