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首页> 外文期刊>Journal of Cellular Physiology >Divergent stress responses to IL-1beta, nitric oxide, and tunicamycin by chondrocytes.
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Divergent stress responses to IL-1beta, nitric oxide, and tunicamycin by chondrocytes.

机译:发散IL-1beta应激反应,硝酸由软骨细胞氧化,衣霉素。

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摘要

As the only cell in cartilage responsible for matrix synthesis, the chondrocyte's viability is crucial to healthy tissue. It must tolerate stresses from both mechanical and cellular sources. This study examines the endoplasmic reticulum (ER) stress response in chondrocytes after exposure to IL-1beta, nitric oxide, or tunicamycin in order to determine whether this form of stress causes cell death. Cultures of the immortalized human juvenile costal chondrocyte cell line, C-28/I2, were treated with IL-1beta, S-nitroso-N-acetylpenicillamine (SNAP), and tunicamycin. Increasing intracellular nitric oxide levels by SNAP treatment or inhibiting protein folding in the ER lumen by tunicamycin induced the ER stress response as evidenced by increased protein and gene expression of GADD153 as well as PERK and eIF2-alpha phosphorylation, and resulted in apoptosis. IL-1beta treatment induced PERK and eIF2-alpha phosphorylation, but not GADD153 expression or apoptosis. The ER stress signaling pathway of IL-1beta involved iNOS because blocking its expression, inhibited ER stress gene expression. Therefore, inducing the ER stress response in chondrocytes results in divergent responses depending on the agent used. Even though IL-1beta, a common proinflammatory cytokine, induces the ER stress response, it is not proapoptotic to chondrocytes. On the other hand, exposure to high levels of intracellular nitric oxide induce chondrocyte apoptosis as part of the ER stress response.
机译:软骨中唯一的细胞负责矩阵合成、软骨细胞的可行性健康组织的关键。强调机械和细胞来源。网(ER)在软骨细胞应激反应接触IL-1beta之后,一氧化氮,或者衣霉素来确定这一点形式的压力会导致细胞死亡。不灭的人类少年肋软骨细胞细胞系,C-28 / I2 IL-1beta处理,S-nitroso-N-acetylpenicillamine(吸附)衣霉素。氧化水平快速治疗或抑制蛋白质折叠的ER腔衣霉素诱导ER应激反应就是明证增加GADD153的蛋白质和基因表达活跃和eIF2-alpha磷酸化,,导致细胞凋亡。诱导活跃和eIF2-alpha磷酸化,但是不是GADD153表达式或凋亡。所涉及的IL-1beta压力信号通路伊诺因为阻塞其表达,抑制ER应激基因表达。软骨细胞ER应激反应的结果不同的反应取决于所使用的代理。尽管IL-1beta,共同促炎细胞因子,导致ER应激反应,它是不proapoptotic软骨细胞。一方面,暴露于高水平的细胞内一氧化氮诱导软骨细胞凋亡作为的ER应激反应。

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