A Comparative Proteomic Analysis of HepG2 Cells Incubated by S(−) and R(+) Enantiomers of Anti‐coagulating Drug Warfarin
Proteomics(2010)
Abstract
Warfarin is a commonly prescribed oral anti‐coagulant with narrow therapeutic index. It interferes with vitamin K cycle to achieve anti‐coagulating effects. Warfarin has two enantiomers, S(−) and R(+) and undergoes stereoselective metabolism, with the S(−) enantiomer being more effective. We reported that the intracellular protein profile in HepG2 cells incubated with S(−) and R(+) warfarin, using iTRAQ‐coupled 2‐D LC‐MS/MS. In samples incubated with S(−) and R(+) warfarin alone, the multi‐task protein Protein SET showed significant elevation in cells incubated with S(−) warfarin but not in those incubated with R(+) warfarin. In cells incubated with individual enantiomers of warfarin in the presence of vitamin K, protein disulfide isomerase A3 which is known as a glucose‐regulated protein, in cells incubated with S(−) warfarin was found to be down‐regulated compared to those incubated with R(+) warfarin. In addition, Protein DJ‐1 and 14‐3‐3 Proteinσ were down‐regulated in cells incubated with either S(−) or R(+) warfarin regardless of the presence of vitamin K. Our results indicated that Protein DJ‐1 may act as an enzyme for expression of essential enzymes in vitamin K cycle. Taken together, our findings provided molecular evidence on a comprehensive protein profile on warfarin–cell interaction, which may shed new lights on future improvement of warfarin therapy.
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Key words
Cell biology,ERp 57,iTRAQ-coupled LC-MS/MS proteomics,Protein DJ-1,14-3-3 Sigma,Warfarin enantiomers
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