A comparative proteomic analysis of HepG2 cells incubated by S(−) and R(+) enantiomers of anti‐coagulating drug warfarin |
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Authors: | Jing Bai Laleh Sadrolodabaee Chi Bun Ching Balram Chowbay Wei Ning Chen |
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Institution: | 1. School of Chemical and Biomedical Engineering, College of Engineering, Nanyang, Technological University, Singapore, Singapore;2. Division of Medical Sciences, Humphrey Oei Institute of Cancer Research National Cancer Centre, Singapore, Singapore |
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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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Keywords: | Cell biology ERp 57 iTRAQ‐coupled LC‐MS/MS proteomics Protein DJ‐1 14‐3‐3 Sigma Warfarin enantiomers |
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