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丹参酮 IIA 通过激活 HIF-1α 信号通路调节葡萄糖转运蛋白 1 的表达。

Tanshinone IIA regulates expression of glucose transporter 1 via activation of the HIF‑1α signaling pathway.

机构信息

Central Laboratory, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200062, P.R. China.

Department of Cardiovascular Medicine, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200062, P.R. China.

出版信息

Mol Med Rep. 2022 Nov;26(5). doi: 10.3892/mmr.2022.12844. Epub 2022 Sep 7.

Abstract

Tanshinone IIA (Tan 2A) is a lipid‑soluble compound extracted from the Chinese herb Danshen (). It protects neuron and microvascular endothelial cells against hypoxia/ischemia both and however the mechanism is not fully known. Glucose transporter 1 (GLUT‑1) is ubiquitously expressed in all types of tissue in the human body and serves important physiological functions due to its glucose uptake ability. The present study evaluated the role of Tan 2A in regulating GLUT‑1 expression and its potential mechanism. RT‑PCR and western Blot were used to detect the expression of GLUT‑1. Si RNA mediated knockdown and CHIP assay were used to explore the mechanism of Tan 2A on GLUT‑1expression. Tan 2A treatment induced expression of GLUT‑1 and subsequently increased glucose uptake in endothelial cells (ECs). Furthermore, mRNA expression levels of vascular endothelial cell growth factor, BCL2 interacting protein 3 and enolase 2, which are target genes for hypoxia‑inducible factor‑1α (HIF‑1α), were significantly upregulated by Tan 2A. Co‑immunoprecipitation demonstrated that Tan 2A markedly increased the association of HIF‑1α with recombination signal‑binding protein for immunoglobulin κJ region (RBPJκ). Moreover, knockdown of HIF‑1α and RBPJκ significantly reversed the regulatory effect of Tan 2A on mRNA expression levels of these genes in ECs. The results of the present study suggested that HIF‑1α partially mediated the regulatory effect of Tan 2A on GLUT‑1 expression in ECs. Therefore, GLUT‑1 may be a potential therapeutic target for Tan 2A.

摘要

丹参酮 IIA(Tan 2A)是一种从中药丹参中提取的脂溶性化合物。它可以保护神经元和微血管内皮细胞免受缺氧/缺血的影响,但其机制尚不完全清楚。葡萄糖转运蛋白 1(GLUT-1)在人体所有类型的组织中广泛表达,由于其摄取葡萄糖的能力,具有重要的生理功能。本研究评估了 Tan 2A 调节 GLUT-1 表达的作用及其潜在机制。RT-PCR 和 Western Blot 用于检测 GLUT-1 的表达。SiRNA 介导的敲低和 CHIP 测定用于探索 Tan 2A 对 GLUT-1 表达的作用机制。Tan 2A 处理诱导 GLUT-1 的表达,随后增加内皮细胞(ECs)中的葡萄糖摄取。此外,血管内皮细胞生长因子、BCL2 相互作用蛋白 3 和烯醇酶 2 的 mRNA 表达水平,这些是缺氧诱导因子-1α(HIF-1α)的靶基因,也被 Tan 2A 显著上调。共免疫沉淀表明,Tan 2A 明显增加了 HIF-1α 与免疫球蛋白 κJ 区重组信号结合蛋白(RBPJκ)的结合。此外,HIF-1α 和 RBPJκ 的敲低显著逆转了 Tan 2A 对 ECs 中这些基因的 mRNA 表达水平的调节作用。本研究结果表明,HIF-1α 部分介导了 Tan 2A 对 ECs 中 GLUT-1 表达的调节作用。因此,GLUT-1 可能是 Tan 2A 的潜在治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8513/9727584/f9eceee2b070/mmr-26-05-12844-g00.jpg

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