Auranofin Inhibits Retinal Pigment Epithelium Cell Survival through Reactive Oxygen Species-Dependent Epidermal Growth Factor Receptor/ Mitogen-Activated Protein Kinase Signaling Pathway.
Auranofin Inhibits Retinal Pigment Epithelium Cell Survival through Reactive Oxygen Species-Dependent Epidermal Growth Factor Receptor/ Mitogen-Activated Protein Kinase Signaling Pathway.
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金诺芬通过活性氧依赖性表皮生长因子受体/丝裂原激活蛋白激酶信号通路抑制视网膜色素上皮细胞存活
DOI：
10.1371/journal.pone.0166386
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发表时间：
2016
期刊：
影响因子：
3.7
通讯作者：
Li W
中科院分区：
文献类型：
--
作者：
Chen X;Tzekov R;Su M;Hong H;Min W;Han A;Li W
视网膜色素上皮（RPE）细胞的异常存活有助于增殖性玻璃体视网膜病变（PVR）的发病机制，PVR是一种视力威胁疾病。在这项研究中，我们探讨了抗风湿剂金糠蛋白（AF）对RPE细胞存活的影响，并研究了其潜在的体外信号机制。结果表明，AF对ARPE-19细胞的存活具有剂量依赖性和时间依赖性。AF的应用诱导了几种效应：表皮生长因子受体（EGFR）总量显著降低，磷酸化的EGFR和丝裂原活化蛋白激酶（MAPK）显著增加，包括细胞外信号调节激酶（ERK）、P38丝裂原活化蛋白激酶（P38MAPK）、c-Jun n端激酶（JNK）、c-Jun、丝裂原活化蛋白激酶活化蛋白激酶2（MAPKAPK2）和热休克蛋白27 （HSP27）。AF还通过影响EGFR/MAPK信号传导抑制表皮生长因子（EGF）依赖性细胞的增殖和迁移。抗氧化剂n -乙酰半胱氨酸（NAC）可阻断af诱导的活性氧（ROS）生成增加、总EGFR降低以及EGFR/MAPK信号通路中多个节点的磷酸化。P38MAPK抑制剂SB203580抑制af诱导的EGFR/ P38MAPK /MAPKAPK2/Hsp27磷酸化，而EGFR （erlotinib）、ERK （FR180204）和JNK （SP600125）抑制剂则不抑制。综上所述，ros依赖性的EGFR/MAPK磷酸化是AF诱导的RPE细胞存活抑制的重要信号通路，AF可能具有治疗PVR中RPE细胞异常存活的潜力。
Abnormal survival of retinal pigment epithelium (RPE) cells contributes to the pathogenesis of proliferative vitreoretinopathy (PVR), a sight-threatening disease. In this study, we explored the effect of the anti-rheumatic agent auranofin (AF) on RPE cell survival and studied the underlying signaling mechanisms in vitro. Our results showed that AF inhibited ARPE-19 cell survival in a dose and time-dependent manner. Application of AF induced several effects: a significant decrease in total epidermal growth factor receptor (EGFR) and an increase in phosphorylated EGFR and mitogen-activated protein kinase (MAPK), including extracellular signal-regulated kinase (ERK), P38 mitogen-activated protein kinase (P38MAPK), c-Jun N-terminal kinase (JNK), c-Jun, mitogen activated protein kinase activated protein kinase 2(MAPKAPK2), and heat shock protein 27 (HSP27). AF also inhibited epidermal growth factor (EGF)-dependent cell proliferation and migration through affecting EGFR/MAPK signaling. The antioxidant N-acetylcysteine (NAC) blocked the AF-induced increase of reactive oxygen species (ROS) production, the reduction of total EGFR, and the phosphorylation of multiple nodes in EGFR/MAPK signaling pathway. P38MAPK inhibitor SB203580, but not inhibitors of EGFR (erlotinib), ERK (FR180204) and JNK (SP600125), suppressed AF-induced phosphorylation of EGFR/p38MAPK/MAPKAPK2/Hsp27. In conclusion, the ROS-dependent phosphorylation of EGFR/MAPK is an important signaling pathway for AF-induced inhibition of RPE cell survival, and AF may have the potential for treatment of abnormal survival of RPE cells in PVR.
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影响因子：
4.6
作者：
Morescalchi F;Duse S;Gambicorti E;Romano MR;Costagliola C;Semeraro F
通讯作者：
Semeraro F
影响因子：
3
作者：
Roder, Christine;Thomson, Melanie J
通讯作者：
Thomson, Melanie J
影响因子：
3.7
作者：
Filosto S;Khan EM;Tognon E;Becker C;Ashfaq M;Ravid T;Goldkorn T
通讯作者：
Goldkorn T
影响因子：
2.1
作者：
BAUDOUIN, C;FREDJREYGROBELLET, D;GASTAUD, P
通讯作者：
GASTAUD, P
影响因子：
27.4
作者：
FINKELSTEIN, AE;WALZ, DT;MISHER, A
通讯作者：
MISHER, A