Prion infection correlates with hypersensitivity of P2X7 nucleotide receptor in a mouse microglial cell line

Prion infection correlates with hypersensitivity of P2X7 nucleotide receptor in a mouse microglial cell line
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DOI:
10.1016/j.febslet.2007.05.057
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发表时间:
2007-06
期刊:
影响因子:
3.5
通讯作者:
T. Takenouchi;Y. Iwamaru;M. Imamura;N. Kato;S. Sugama;M. Fujita;M. Hashimoto;Mitsuru Sato;H. Okada;T. Yokoyama;S. Mohri;H. Kitani
T. Takenouchi;Y. Iwamaru;M. Imamura;N. Kato;S. Sugama;M. Fujita;M. Hashimoto;Mitsuru Sato;H. Okada;T. Yokoyama;S. Mohri;H. Kitani
中科院分区:
生物学3区
文献类型:
--
作者:
T. Takenouchi;Y. Iwamaru;M. Imamura;N. Kato;S. Sugama;M. Fujita;M. Hashimoto;Mitsuru Sato;H. Okada;T. Yokoyama;S. Mohri;H. Kitani

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我们最近建立了小鼠小胶质细胞持续感染小鼠适应痒病ME7 (ScMG20/ME7),用于体外研究朊病毒的发病机制。在这里,我们发现ScMG20/ME7细胞对P2X7受体激动剂过敏,通过持续的Ca2+内流、膜孔形成、细胞死亡和白细胞介素-1β释放来证明。P2X7 mRNA在这些细胞中表达上调,也在瘙痒病感染小鼠的大脑中表达上调。用聚硫酸戊聚糖处理消除了ScMG20/ME7细胞培养物中的传染性和疾病相关形式的朊病毒蛋白,但P2X7受体的超敏反应仍然存在。这些结果表明,朊病毒感染可能强烈影响小鼠小胶质细胞的P2X7受体系统。
We recently established mouse microglial cells persistently infected with mouse-adapted scrapie ME7 (ScMG20/ME7) for in vitro study of prion pathogenesis. Here, we found that ScMG20/ME7 cells were hypersensitive to P2X7 receptor agonists, as demonstrated by sustained Ca2+influx, membrane pore formation, cell death, and interleukin-1β release. P2X7 mRNA expression was upregulated in these cells, and also in scrapie-infected mice brains. Treatment with pentosan polysulfate eliminated the infectivity and disease-related forms of prion protein from ScMG20/ME7 cell cultures, however, hypersensitivity of P2X7 receptors remained. These results suggest that prion infections may strongly affect the P2X7 receptor system in mouse microglial cells.