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甜菊醇、甜菊糖苷和甜菊提取物对正常和癌细胞中糖皮质激素受体信号的影响。

Effect of steviol, steviol glycosides and stevia extract on glucocorticoid receptor signaling in normal and cancer blood cells.

机构信息

Department of Clinical Biochemistry, Medical School, National and Kapodistrian University of Athens, University General Hospital "ATTIKO", Athens, Greece.

Department of Biological Chemistry, Medical School, National and Kapodistrian University of Athens, Athens, Greece.

出版信息

Mol Cell Endocrinol. 2018 Jan 15;460:189-199. doi: 10.1016/j.mce.2017.07.023. Epub 2017 Jul 25.

Abstract

The use of steviol glycosides as non-caloric sweeteners has proven to be beneficial for patients with type 2 diabetes mellitus (T2D), obesity, and metabolic syndrome. However, recent data demonstrate that steviol and stevioside might act as glucocorticoid receptor (GR) agonists and thus correlate with adverse effects on metabolism. Herein, we evaluated the impact of steviol, steviol glycosides, and a Greek-derived stevia extract on a number of key steps of GR signaling cascade in peripheral blood mononuclear cells (PBMCs) and in Jurkat leukemia cells. Our results revealed that none of the tested compounds altered the expression of primary GR-target genes (GILZ, FKPB5), GR protein levels or GR subcellular localization in PBMCs; those compounds increased GILZ and FKPB5 mRNA levels as well as GRE-mediated luciferase activity, inducing in parallel GR nuclear translocation in Jurkat cells. The GR-modulatory activity demonstrated by stevia-compounds in Jurkat cells but not in PBMCs may be due to a cell-type specific effect.

摘要

甜菊醇糖苷作为非热量甜味剂的使用已被证明对 2 型糖尿病(T2DM)、肥胖症和代谢综合征患者有益。然而,最近的数据表明,甜菊醇和甜菊苷可能作为糖皮质激素受体(GR)激动剂,从而与对代谢的不良影响相关。在此,我们评估了甜菊醇、甜菊醇糖苷和一种源自希腊的甜菊提取物对外周血单个核细胞(PBMC)和 Jurkat 白血病细胞中 GR 信号级联的多个关键步骤的影响。我们的结果表明,在 PBMC 中,没有一种测试化合物改变主要的 GR 靶基因(GILZ、FKPB5)、GR 蛋白水平或 GR 亚细胞定位的表达;这些化合物增加了 GILZ 和 FKPB5 的 mRNA 水平以及 GRE 介导的荧光素酶活性,同时诱导 Jurkat 细胞中 GR 的核转位。甜菊醇糖苷在 Jurkat 细胞而非 PBMC 中表现出的 GR 调节活性可能是由于细胞类型特异性效应。

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