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岩藻聚糖硫酸酯抑制 G 蛋白偶联受体激动剂诱导的 Ca2+反应。

Fucoidan inhibits Ca2+ responses induced by a wide spectrum of agonists for G‑protein‑coupled receptors.

机构信息

Laboratory of Cell Imaging, Henan University of Chinese Medicine, Zhengzhou, Henan 450002, P.R. China.

The Research Institute of The McGill University Health Centre, Montreal, QC H4A 3J1, Canada.

出版信息

Mol Med Rep. 2018 Jan;17(1):1428-1436. doi: 10.3892/mmr.2017.8035. Epub 2017 Nov 13.

Abstract

Fucoidan, a sulfated polysaccharide extracted from brown seaweed, has been used in traditional Chinese herbal medicine to treat thyroid tumors for many years. Although a number of its cellular effects have been investigated, the role of fucoidan in molecular signaling, particularly in Ca2+ signaling, remains largely unknown. In the present study, the effects of fucoidan on Ca2+ responses in HeLa cells, human umbilical vein endothelial cells and astrocytes were investigated using a wide range of receptor agonists. Fucoidan inhibited the increase in intracellular free calcium concentration that was induced by histamine, ATP, compound 48/80 and acetylcholine. The responses induced by the same agonists in the absence of extracellular Ca2+ were also markedly suppressed by fucoidan. Reverse transcription‑polymerase chain reaction demonstrated that 0.5 and 1.0 mg/ml fucoidan treatment for 3 h decreased histamine receptor 1 expression in HeLa cells. Similarly, the expressions of purinergic receptor P2Y, G‑protein coupled (P2YR)1, P2YR2 and P2YR11 were significantly downregulated within cells pretreated with 1.0 mg/ml fucoidan for 3 h, and 0.5 mg/ml fucoidan significantly inhibited P2YR1 and P2YR11 expression. The results demonstrated that fucoidan may exert a wide spectrum of inhibitory effects on Ca2+ responses and that fucoidan may inhibit a number of different G‑protein coupled receptors associated with Ca2+ dynamics.

摘要

岩藻聚糖硫酸酯是一种从褐藻中提取的硫酸多糖,多年来一直被用于中药治疗甲状腺肿瘤。尽管已经研究了它的许多细胞作用,但岩藻聚糖硫酸酯在分子信号转导中的作用,特别是在 Ca2+信号转导中的作用,在很大程度上仍然未知。在本研究中,使用广泛的受体激动剂研究了岩藻聚糖硫酸酯对 HeLa 细胞、人脐静脉内皮细胞和星形胶质细胞中 Ca2+反应的影响。岩藻聚糖硫酸酯抑制了组胺、ATP、化合物 48/80 和乙酰胆碱诱导的细胞内游离钙浓度的增加。在没有细胞外 Ca2+的情况下,相同激动剂诱导的反应也被岩藻聚糖硫酸酯显著抑制。逆转录-聚合酶链反应表明,0.5 和 1.0 mg/ml 岩藻聚糖硫酸酯处理 3 h 可降低 HeLa 细胞中组胺受体 1 的表达。同样,在用 1.0 mg/ml 岩藻聚糖硫酸酯预处理 3 h 的细胞中,嘌呤能受体 P2Y、G-蛋白偶联(P2YR)1、P2YR2 和 P2YR11 的表达显著下调,而 0.5 mg/ml 岩藻聚糖硫酸酯显著抑制 P2YR1 和 P2YR11 的表达。结果表明,岩藻聚糖硫酸酯可能对 Ca2+反应产生广泛的抑制作用,并且岩藻聚糖硫酸酯可能抑制与 Ca2+动力学相关的许多不同的 G-蛋白偶联受体。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/173e/5780082/85ff6d76af8f/MMR-17-01-1428-g00.jpg

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