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谷氧还蛋白1(GRX1)通过调节骨关节炎中CREB/HO-1抑制软骨细胞的氧化应激和凋亡。

Glutaredoxin 1 (GRX1) inhibits oxidative stress and apoptosis of chondrocytes by regulating CREB/HO-1 in osteoarthritis.

作者信息

Sun Jie, Wei Xuelei, Lu Yandong, Cui Meng, Li Fangguo, Lu Jie, Liu Yunjiao, Zhang Xi

机构信息

Department of Orthopaedic Trauma, Tianjin Hospital, Tianjin, 300211, China.

Department of Orthopaedic Trauma, Tianjin Hospital, Tianjin, 300211, China.

出版信息

Mol Immunol. 2017 Oct;90:211-218. doi: 10.1016/j.molimm.2017.08.006. Epub 2017 Aug 23.

Abstract

GRX1 (glutaredoxin1), a sulfhydryl disulfide oxidoreductase, is involved in many cellular processes, including anti-oxidation, anti-apoptosis, and regulation of cell differentiation. However, the role of GRX1 in the oxidative stress and apoptosis of osteoarthritis chondrocytes remains unclear, prompting the current study. Protein and mRNA expressions were measured by Western blot and RT-qPCR. Oxidative stress was detected by the measurement of MDA and SOD contents. Cells apoptosis were detected by Annexin V-FITC/PI and caspase-3 activity assays. We found that the mRNA and protein expressions of GRX1 were significantly down-regulated in osteoarthritis tissues and cells. GRX1 overexpression increased the mRNA and protein expression of CREB and HO-1. Meanwhile, GRX1 overexpression inhibited oxidative stress and apoptosis in osteoarthritis chondrocytes. Furthermore, we found that GRX1 overexpression regulated HO-1 by increasing CREB, and that HO-1 regulated oxidative stress and apoptosis in osteoarthritis chondrocytes. Thus, GRX1 overexpression constrains oxidative stress and apoptosis in osteoarthritis chondrocytes by regulating CREB/HO-1, providing a novel insight into the molecular mechanism and potential treatment of osteoarthritis.

摘要

谷氧还蛋白1(GRX1)是一种巯基二硫键氧化还原酶,参与包括抗氧化、抗凋亡以及细胞分化调控在内的多种细胞过程。然而,GRX1在骨关节炎软骨细胞氧化应激和凋亡中的作用仍不清楚,这促使了当前的研究。通过蛋白质免疫印迹法和逆转录定量聚合酶链反应(RT-qPCR)检测蛋白质和mRNA表达。通过测量丙二醛(MDA)和超氧化物歧化酶(SOD)含量来检测氧化应激。通过膜联蛋白V-异硫氰酸荧光素/碘化丙啶(Annexin V-FITC/PI)和半胱天冬酶-3活性测定来检测细胞凋亡。我们发现,GRX1的mRNA和蛋白质表达在骨关节炎组织和细胞中显著下调。GRX1过表达增加了环磷腺苷效应元件结合蛋白(CREB)和血红素氧合酶-1(HO-1)的mRNA和蛋白质表达。同时,GRX1过表达抑制了骨关节炎软骨细胞的氧化应激和凋亡。此外,我们发现GRX1过表达通过增加CREB来调节HO-1,并且HO-1调节骨关节炎软骨细胞的氧化应激和凋亡。因此,GRX1过表达通过调节CREB/HO-1抑制骨关节炎软骨细胞的氧化应激和凋亡,为骨关节炎的分子机制和潜在治疗提供了新的见解。

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