Enhancement of Protein Kinase C-mediated EGF Receptor Phosphorylation by Auranofin

Froscio, Mario; Murray, Andrew J.; Np, Hurst

doi:10.3109/03009748809098797

Cited by 6 publications

(2 citation statements)

References 18 publications

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“…Some data suggested that the ERK activation mediated by EGFR plays an active role in oxidative stress-induced apoptosis of cells [31] and oxidative stress-dependent activation of JNK and P38MAPK is also involved in cell apoptosis [32,33]. Froscio et al have demonstrated that AF enhanced the phosphorylation of EGFR in the epidermoid carcinoma cell lines [15]. Some studies also showed that AF caused phosphorylation of P38MAPK, ERK, JNK, and MAPKAPK2 [16,17], however, whether similar processes occur in RPE cells is not clear.…”

Section: Discussionmentioning

confidence: 99%

“…Some data suggest that AF has also potential for the treatment of other diseases, such as cancer, neurodegenerative disorders and infectious diseases [13]. Studies have showed that AF inhibited EGF binding to HeLa cells and enhanced protein kinase C-mediated EGFR phosphorylation in epidermoid carcinoma cell line [14,15]. It was also reported that AF can activate different kinases participating in signaling cascades controlling cellular responses to cytokines and stress, like P38MAPK, ERK, and JNK [16,17].…”

Section: Introductionmentioning

confidence: 99%

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Auranofin Inhibits Retinal Pigment Epithelium Cell Survival through Reactive Oxygen Species-Dependent Epidermal Growth Factor Receptor/ Mitogen-Activated Protein Kinase Signaling Pathway

Chen

Tzekov

et al. 2016

PLoS ONE

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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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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Auranofin Inhibits Retinal Pigment Epithelium Cell Survival through Reactive Oxygen Species-Dependent Epidermal Growth Factor Receptor/ Mitogen-Activated Protein Kinase Signaling Pathway

Chen

Tzekov

et al. 2016

PLoS ONE

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Antirheumatic gold compounds and penicillamine enhance protein kinase C-mediated activation of the arachidonate- mobilizing phospholipase A2 in mouse macrophages

Bondeson

Sundler²

1993

Journal of Leukocyte Biology

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The effects of antirheumatic gold compounds and D-penicillamine on protein kinase C- and Ca(2+)-mediated activation of arachidonate mobilization and the formation of eicosanoids in mouse macrophages have been investigated. Auranofin (0.2-2 microM) enhanced the response to phorbol ester two- to three-fold, and similar enhancement was caused by aurothiomalate, aurothioglucose, and penicillamine, but only after pretreatment for 1-4 h. The enhanced mobilization of arachidonate was accompanied by increased formation and release of prostaglandin E2 and 6-keto prostaglandin F1 alpha, but not of lipoxygenase metabolites. No such enhancement occurred when the arachidonate-mobilizing phospholipase A2 was activated directly (calcium ionophore A23187). Instead, auranofin caused selective inhibition of calcium ionophore-induced formation of leukotriene C4. Treatment of macrophages with 4 beta-phorbol 12-myristate 13-acetate causes a rapid increase in the phosphorylation and a 1.4-1.8-fold increase in the activity of the 85-kd arachidonate-mobilizing phospholipase A2 as determined in an in vitro assay. The increase in activity was further enhanced by both the gold compounds and penicillamine. These findings indicate that the target for the enhancing effect of the antirheumatic drugs is located between protein kinase C and phospholipase A2 in the signal chain leading to activation of the latter enzyme.

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Inhibition of protein kinase C activity by the antirheumatic drug auranofin

Froscio

Murray²,

Hurst

1989

Biochemical Pharmacology

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Enhancement of Protein Kinase C-mediated EGF Receptor Phosphorylation by Auranofin

Cited by 6 publications

References 18 publications

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

Antirheumatic gold compounds and penicillamine enhance protein kinase C-mediated activation of the arachidonate- mobilizing phospholipase A2 in mouse macrophages

Inhibition of protein kinase C activity by the antirheumatic drug auranofin

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