Expression and regulation of the proton-coupled oligopeptide transporter PhT2 by LPS in macrophages and mouse spleen.

Expression and regulation of the proton-coupled oligopeptide transporter PhT2 by LPS in macrophages and mouse spleen.
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DOI:
10.1021/mp500014r
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发表时间:
2014-06-02
影响因子:
4.9
通讯作者:
Jiang H
Jiang H
中科院分区:
医学2区
文献类型:
--
作者:
Wang Y;Sun D;Song F;Hu Y;Smith DE;Jiang H

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膜转运蛋白PhT 2(SLC 15 A3)属于质子偶联寡肽转运蛋白家族,利用向内定向的质子梯度和负膜电位介导二肽/三肽和组氨酸的转运。本研究的目的是阐明PhT 2在巨噬细胞和小鼠组织中的分子表达,并探讨脂多糖(LPS)对PhT 2的调节。结果显示PhT 2在J774A.1和THP-1巨噬细胞、小鼠脾和肺中相对高的表达。利用LPS诱导的炎症细胞模型,我们发现hPhT 2 mRNA在THP-1细胞中表达上调,而NF-κB的特异性抑制剂吡咯烷二硫代氨基甲酸酯(pyrrolidine dithiocarbamate)可抑制这种上调。在LPS诱导的急性炎症期间,在小鼠脾脏中观察到类似的结果。使用双标记免疫荧光和共聚焦激光扫描显微镜,我们证实了mPhT 2与溶酶体相关膜蛋白1在转染的HEK 293细胞中共定位。这些结果提示LPS通过NF-κB信号通路上调了溶酶体膜转运蛋白PhT 2的表达。
Membrane transporter PhT2 (SLC15A3), which belongs to the proton-coupled oligopeptide transporter family, mediates the transport of di/tripeptides and histidine utilizing an inwardly directed proton gradient and negative membrane potential. The aim of this study was to elucidate the molecular expression of PhT2 in macrophages and mouse tissues and to explore the regulation of PhT2 by lipopolysaccharide (LPS). The results showed relatively high expression of PhT2 in J774A.1 and THP-1 macrophage cells, mouse spleen, and lung. Using an LPS-induced inflammatory cell model, we found that hPhT2 mRNA expression was up-regulated in THP-1 cells and that the up-regulation was suppressed by pyrrolidine dithiocarbamate, a specific inhibitor of NF-κB. Similar results were observed in mouse spleen during LPS-induced acute inflammation. Using dual-labeling immunofluorescence and confocal laser scanning microscopy, we confirmed that mPhT2 was colocalizing with lysosome-associated membrane protein 1 in transfected HEK293 cells. These results suggested that PhT2, a lysosomal membrane transporter, was up-regulated by LPS via the NF-κB signaling pathway.
质子偶联寡肽转运蛋白(POT)在小鼠前列腺以及良性前列腺增生(BPH)和前列腺癌(PCa)患者中的表达
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