Glutamine starvation enhances PCV2 replication via the phosphorylation of p38 MAPK, as promoted by reducing glutathione levels.

Glutamine starvation enhances PCV2 replication via the phosphorylation of p38 MAPK, as promoted by reducing glutathione levels.
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谷氨酰胺饥饿通过 p38 MAPK 磷酸化增强 PCV2 复制,降低谷胱甘肽水平可促进 PCV2 复制。

DOI:
10.1186/s13567-015-0168-1
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发表时间:
2015-03-18
影响因子:
4.4
通讯作者:
Huang K
Huang K
中科院分区:
农林科学2区
文献类型:
--
作者:
Chen X;Shi X;Gan F;Huang D;Huang K

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谷氨酰胺对改善猪圆环病毒2型(PCV2)引起的生殖障碍有积极作用。然而,谷氨酰胺影响PCV2复制的机制尚不清楚。本研究旨在探讨谷氨酰胺对PCV2病毒复制的影响及其机制。结果表明,谷氨酰胺对PK-15细胞有促进作用。令人惊讶的是,谷氨酰胺饥饿显著增加了PCV2的复制。加入含4 mM谷氨酰胺的新鲜培养基后,谷氨酰胺饥饿对PCV2复制的促进作用消失。同样,加入丁硫氨酸亚磺胺(BSO)后,PCV2也有促进作用。谷氨酰胺饥饿或BSO处理可增加PK-15细胞p38MAPK的磷酸化水平和PCV2的复制。同时,p38基因敲除的PK-15细胞中p38MAPK磷酸化和PCV2复制显著降低。在p38基因敲除的PK-15细胞中,谷氨酰胺饥饿引起的PCV2复制的促进作用可能被阻断。因此,谷氨酰胺饥饿通过促进p38MAPK的激活来增加PCV2的复制,这与细胞内谷胱甘肽水平的下调有关。我们的发现可能有助于解释PCV2的可能致病机制,并为谷氨酰胺在控制猪圆环病毒相关疾病中的应用提供理论参考。
Glutamine has a positive effect on ameliorating reproductive failure caused by porcine circovirus type 2 (PCV2). However, the mechanism by which glutamine affects PCV2 replication remains unclear. This study was conducted to investigate the effects of glutamine on PCV2 replication and its underlying mechanisms in vitro. The results show that glutamine promoted PK-15 cell viability. Surprisingly, glutamine starvation significantly increased PCV2 replication. The promotion of PCV2 replication by glutamine starvation disappeared after fresh media with 4 mM glutamine was added. Likewise, promotion of PCV2 was observed after adding buthionine sulfoximine (BSO). Glutamine starvation or BSO treatment increased the level of p38 MAPK phosphorylation and PCV2 replication in PK-15 cells. Meanwhile, p38 MAPK phosphorylation and PCV2 replication significantly decreased in p38-knockdown PK-15 cells. Promotion of PCV2 replication caused by glutamine starvation could be blocked in p38-knockdown PK-15 cells. Therefore, glutamine starvation increased PCV2 replication by promoting p38 MAPK activation, which was associated with the down regulation of intracellular glutathione levels. Our findings may contribute toward interpreting the possible pathogenic mechanism of PCV2 and provide a theoretical reference for application of glutamine in controlling porcine circovirus-associated diseases.
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