Pharmacological impairment of s-nitrosoglutathione or thioredoxin reductases augments protein S-Nitrosation in human hepatocarcinoma cells
العنوان: | Pharmacological impairment of s-nitrosoglutathione or thioredoxin reductases augments protein S-Nitrosation in human hepatocarcinoma cells |
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المؤلفون: | Lopez-Sanchez, Laura M., Corrales, Fernando J., CHARY LOPEZ-PEDRERA, Aranda, Enrique, Rodriguez-Ariza, Antonio |
المصدر: | Europe PubMed Central ResearcherID |
مصطلحات موضوعية: | Thioredoxin-Disulfide Reductase/metabolism, Auranofin/pharmacology, S-Nitrosoglutathione/metabolism, Proteins/metabolism, Plicamycin/analogs & derivatives, Thioredoxin-Disulfide Reductase/antagonists & inhibitors |
الوصف: | BACKGROUND/AIM: S-Nitrosoglutathione reductase (GSNOR) and thioredoxin enzyme systems participate in cellular defence against nitrosative stress. Pharmacological interventions against these enzyme systems might represent valuable strategies to impair S-nitrosothiol (SNO) homeostasis in tumour cells. MATERIALS AND METHODS: Human HepG2 cells were pre-treated with mithramycin A or auranofin and exposed to S-nitroso-L-cysteine. GSNOR mRNA levels were analyzed by quantitative real-time reverse transcriptase-polymerase chain reaction and S-nitrosated proteins were detected and purified using the biotin-switch approach. Proteins were identified using electrospray ionization tandem mass spectrometry. RESULTS: Mithramycin interfered with GSNOR induction resulting in an increased cellular sensitivity to protein S-nitrosation. Moreover, the thioredoxin reductase inhibitor auranofin also increased cellular susceptibility to S-nitrosoprotein formation. The impairment of these two cellular defense systems against nitrosative stress resulted in different sets of S-nitrosated proteins, as revealed by the proteomics approach. CONCLUSION: Our results suggest that pharmacological intervention with mithramycin or auranofin may constitute promising tools for altering SNO homeostasis in tumour cells. |
URL الوصول: | https://explore.openaire.eu/search/publication?articleId=dedup_wf_001::a97d080626b6ea505036cde90999e113 http://europepmc.org/abstract/med/20332448 |
حقوق: | CLOSED |
رقم الأكسشن: | edsair.dedup.wf.001..a97d080626b6ea505036cde90999e113 |
قاعدة البيانات: | OpenAIRE |
الوصف غير متاح. |