Pharmacological impairment of s-nitrosoglutathione or thioredoxin reductases augments protein S-Nitrosation in human hepatocarcinoma cells
Keywords: 
Auranofin/pharmacology
Plicamycin/analogs & derivatives
Proteins/metabolism
S-Nitrosoglutathione/metabolism
Thioredoxin-Disulfide Reductase/antagonists & inhibitors
Thioredoxin-Disulfide Reductase/metabolism
Issue Date: 
2010
Publisher: 
International Institute of Anticancer Research
ISSN: 
1791-7530
Citation: 
Lopez-Sanchez LM, Corrales FJ, Lopez-Pedrera C, Aranda E, Rodriguez-Ariza A. Pharmacological impairment of s-nitrosoglutathione or thioredoxin reductases augments protein S-Nitrosation in human hepatocarcinoma cells. Anticancer Res 2010 Feb;30(2):415-421.
Abstract
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.

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