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PRDX1 缺失细胞中葡萄糖转运蛋白 GLUT3 的调节改变导致对亚砷酸盐的敏感性增加。

Altered Regulation of the Glucose Transporter GLUT3 in PRDX1 Null Cells Caused Hypersensitivity to Arsenite.

机构信息

College of Health and Life Sciences, Hamad Bin Khalifa University (HBKU), Qatar Foundation (QF), Education City, Doha 34110, Qatar.

Diabetes Research Center, Qatar Biomedical Research Institute (QBRI), Hamad Bin Khalifa University (HBKU), Qatar Foundation (QF), Doha 34110, Qatar.

出版信息

Cells. 2023 Nov 22;12(23):2682. doi: 10.3390/cells12232682.

Abstract

Targeting tumour metabolism through glucose transporters is an attractive approach. However, the role these transporters play through interaction with other signalling proteins is not yet defined. The glucose transporter SLC2A3 (GLUT3) is a member of the solute carrier transporter proteins. GLUT3 has a high affinity for D-glucose and regulates glucose uptake in the neurons, as well as other tissues. Herein, we show that GLUT3 is involved in the uptake of arsenite, and its level is regulated by peroxiredoxin 1 (PRDX1). In the absence of PRDX1, GLUT3 mRNA and protein expression levels are low, but they are increased upon arsenite treatment, correlating with an increased uptake of glucose. The downregulation of GLUT3 by siRNA or deletion of the gene by CRISPR cas-9 confers resistance to arsenite. Additionally, the overexpression of GLUT3 sensitises the cells to arsenite. We further show that GLUT3 interacts with PRDX1, and it forms nuclear foci, which are redistributed upon arsenite exposure, as revealed by immunofluorescence analysis. We propose that GLUT3 plays a role in mediating the uptake of arsenite into cells, and its homeostatic and redox states are tightly regulated by PRDX1. As such, GLUT3 and PRDX1 are likely to be novel targets for arsenite-based cancer therapy.

摘要

通过靶向肿瘤代谢葡萄糖转运蛋白是一种有吸引力的方法。然而,这些转运蛋白通过与其他信号蛋白相互作用所发挥的作用尚未确定。葡萄糖转运蛋白 SLC2A3(GLUT3)是溶质载体转运蛋白家族的成员。GLUT3 对 D-葡萄糖具有高亲和力,调节神经元以及其他组织中的葡萄糖摄取。在此,我们表明 GLUT3 参与亚砷酸盐的摄取,其水平受过氧化物酶 1(PRDX1)调节。在没有 PRDX1 的情况下,GLUT3 mRNA 和蛋白表达水平较低,但在亚砷酸盐处理后增加,与葡萄糖摄取增加相关。通过 siRNA 下调 GLUT3 或通过 CRISPR cas-9 基因编辑删除该基因可赋予细胞对亚砷酸盐的抗性。此外,GLUT3 的过表达使细胞对亚砷酸盐敏感。我们进一步表明,GLUT3 与 PRDX1 相互作用,并通过免疫荧光分析显示,在亚砷酸盐暴露时形成核焦点,随后重新分布。我们提出 GLUT3 在介导亚砷酸盐进入细胞的摄取中发挥作用,其动态平衡和氧化还原状态受 PRDX1 严格调节。因此,GLUT3 和 PRDX1 可能是基于亚砷酸盐的癌症治疗的新靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1edc/10705171/2d7dbb3b245e/cells-12-02682-g001.jpg

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