A comparative proteomic analysis of HepG2 cells incubated by S(-) and R(+) enantiomers of anti-coagulating drug warfarin

作者：Bai Jing; Sadrolodabaee Laleh; Ching Chi Bun; Chowbay Balram; Chen Wei Ning^*

来源：Proteomics, 2010, 10(7): 1463-1473.

DOI：10.1002/pmic.200900785

• Cell biology
• ERp 57
• iTRAQ-coupled LC-MS/MS proteomics
• Protein DJ-1
• 14-3-3 Sigma
• Warfarin enantiomers

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 Protein sigma 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.

• 出版日期2010-4
• 单位南阳理工学院