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白藜芦醇通过抑制磷酸肌醇 3-激酶/蛋白激酶 B 信号通路抑制低氧诱导的肺动脉血管平滑肌细胞增殖和迁移。

Resveratrol inhibits hypoxia-induced proliferation and migration of pulmonary artery vascular smooth muscle cells by inhibiting the phosphoinositide 3-kinase/protein kinase B signaling pathway.

机构信息

Intensive Care Unit, The Third Affiliated Hospital of Qiqihar Medical University, Qiqihar, Heilongjiang 161099, P.R. China.

Emergency Department, The Third Affiliated Hospital of Qiqihar Medical University, Qiqihar, Heilongjiang 161099, P.R. China.

出版信息

Mol Med Rep. 2017 Aug;16(2):1653-1660. doi: 10.3892/mmr.2017.6814. Epub 2017 Jun 20.

Abstract

Hypoxia is a risk factor for severe chronic obstructive pulmonary disease, which aggravates the disease and may cause mortality by inducing hypoxic pulmonary hypertension (HPH). Proliferation and migration of pulmonary artery smooth muscle cells (PASMCs) may mediate this effect. Resveratrol is a phenolic compound extracted from a plant and has been reported to alleviate HPH, although the underlying mechanisms remained to be elucidated. In cancer, resveratrol has been reported to abrogate the phosphoinositide 3‑kinase/protein kinase B (AKT) signaling pathway, thereby inhibiting tumor development. Therefore, the present study aimed to investigate the role of resveratrol in preventing PASMCs from proliferating and migrating. Resveratrol was demonstrated to be inhibitory in a dose‑dependent manner on hypoxia‑induced cell proliferation and migration, and protein expression levels of phosphorylated AKT and AKT. Additionally, resveratrol was identified to act synergistically with LY‑294002, a phosphorylation inhibitor of AKT, but antagonistically with insulin‑like growth factor‑1, an agonist of AKT phosphorylation. This suggested that resveratrol may reduce proliferation and migration by diminishing expression and phosphorylation of AKT, thereby preventing development of HPH.

摘要

缺氧是严重慢性阻塞性肺疾病的一个危险因素,可通过诱导低氧性肺动脉高血压(HPH)使疾病恶化,并可能导致死亡。肺动脉平滑肌细胞(PASMCs)的增殖和迁移可能介导这种作用。白藜芦醇是一种从植物中提取的酚类化合物,据报道可减轻 HPH,尽管其潜在机制仍有待阐明。在癌症中,白藜芦醇已被报道可阻断磷酸肌醇 3-激酶/蛋白激酶 B(AKT)信号通路,从而抑制肿瘤发展。因此,本研究旨在探讨白藜芦醇在防止 PASMC 增殖和迁移中的作用。结果表明,白藜芦醇对缺氧诱导的细胞增殖和迁移以及磷酸化 AKT 和 AKT 的蛋白表达水平呈剂量依赖性抑制作用。此外,白藜芦醇与 AKT 磷酸化的抑制剂 LY-294002 表现出协同作用,但与 AKT 磷酸化的激动剂胰岛素样生长因子-1 表现出拮抗作用。这表明,白藜芦醇可能通过降低 AKT 的表达和磷酸化来减少增殖和迁移,从而预防 HPH 的发生。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c6a3/5562090/d3b7ed6f3550/MMR-16-02-1653-g00.jpg

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