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牛磺酸通过Wnt/β-连环蛋白信号通路对过氧化氢诱导的UMR-106细胞氧化应激的细胞保护作用。

Cytoprotective Effect of Taurine against Hydrogen Peroxide-Induced Oxidative Stress in UMR-106 Cells through the Wnt/β-Catenin Signaling Pathway.

作者信息

Lou Jing, Han Donghe, Yu Huihui, Yu Guang, Jin Meihua, Kim Sung-Jin

机构信息

Department of Immunology, Jinzhou Medical University, Jinzhou 121001, China.

Department of Neurobiology, Jinzhou Medical University, Jinzhou 121001, China.

出版信息

Biomol Ther (Seoul). 2018 Nov 1;26(6):584-590. doi: 10.4062/biomolther.2018.049.

Abstract

Osteoporosis development is closely associated with oxidative stress and reactive oxygen species (ROS). Taurine has potential antioxidant effects, but its role in osteoblasts is not clearly understood. The aim of this study was to determine the protective effects and mechanisms of actions of taurine on hydrogen peroxide (HO)-induced oxidative stress in osteoblast cells. UMR-106 cells were treated with taurine prior to HO exposure. After treatment, cell viability, apoptosis, intracellular ROS production, malondialdehyde content, and alkaline phosphate (ALP) activity were measured. We also investigated the protein levels of β-catenin, ERK, CHOP and NF-E2-related factor 2 (Nrf2) along with the mRNA levels of Nrf2 downstream antioxidants. The results showed that pretreatment of taurine could reverse the inhibition of cell viability and suppress the induced apoptosis in a dose-dependent manner: taurine significantly reduced HO-induced oxidative damage and expression of CHOP, while it induced protein expression of Nrf2 and β-catenin and activated ERK phosphorylation. DKK1, a Wnt/β-catenin signaling inhibitor, significantly suppressed the taurine-induced Nrf2 signaling pathway and increased CHOP. Activation of ERK signaling mediated by taurine in the presence of HO was significantly inhibited by DKK1. These data demonstrated that taurine protects osteoblast cells against oxidative damage via Wnt/β-catenin-mediated activation of the ERK signaling pathway.

摘要

骨质疏松症的发展与氧化应激和活性氧(ROS)密切相关。牛磺酸具有潜在的抗氧化作用,但其在成骨细胞中的作用尚不清楚。本研究的目的是确定牛磺酸对过氧化氢(HO)诱导的成骨细胞氧化应激的保护作用及其作用机制。在HO暴露之前,用牛磺酸处理UMR-106细胞。处理后,测量细胞活力、凋亡、细胞内ROS产生、丙二醛含量和碱性磷酸酶(ALP)活性。我们还研究了β-连环蛋白、ERK、CHOP和核因子E2相关因子2(Nrf2)的蛋白水平以及Nrf2下游抗氧化剂的mRNA水平。结果表明,牛磺酸预处理可以逆转细胞活力的抑制,并以剂量依赖的方式抑制诱导的凋亡:牛磺酸显著降低HO诱导的氧化损伤和CHOP的表达,同时诱导Nrf2和β-连环蛋白的蛋白表达并激活ERK磷酸化。DKK1是一种Wnt/β-连环蛋白信号抑制剂,可显著抑制牛磺酸诱导的Nrf2信号通路并增加CHOP。在HO存在的情况下,DKK1显著抑制了牛磺酸介导的ERK信号通路的激活。这些数据表明,牛磺酸通过Wnt/β-连环蛋白介导的ERK信号通路激活来保护成骨细胞免受氧化损伤。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3cdb/6254645/7784999f0643/bt-26-584f1.jpg

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