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Published on: March 13, 2014
Comparative Proteomics Analysis of Human Liver Microsomes and S9 Fractions
Xinwen Wang1, Bing He1, Jian Shi1
1Department of Clinical Pharmacy, University of Michigan, Ann Arbor, Michigan (X.W., B.H., J.S., H.-J.Z.); and School of Life Science and Technology, China Pharmaceutical University, Nanjing, Jiangsu, China (Q.L.).
This study quantifies proteins in human liver microsomes (HLM) and S9 fractions (HLS9), revealing significant differences in drug-metabolizing enzymes and transporters. These findings aid in selecting appropriate preparations for in vitro drug metabolism studies.
Area of Science:
- Pharmacology
- Proteomics
- Biochemistry
Background:
- Human liver microsomes (HLM) and S9 fractions (HLS9) are vital for in vitro drug metabolism research.
- A quantitative proteomic comparison between HLM and HLS9 is currently lacking, hindering data interpretation and preparation selection.
Purpose of the Study:
- To quantitatively compare the proteomes of HLM and HLS9 from 102 human livers.
- To identify differences in drug-metabolizing enzymes (DMEs) and transporters between HLM and HLS9.
- To provide insights for selecting appropriate hepatic preparations for in vitro drug metabolism studies.
Main Methods:
- Label-free global absolute quantitative proteomics was employed.
- Analysis of HLM and HLS9 proteomes from 102 individual human livers.
- Quantification of 3137 proteins, including DMEs and transporters.
Main Results:
- 3087 proteins were quantified in both HLM and HLS9 with high correlation (R=0.87).
- Significant differences in the abundance of 98 DMEs and 51 transporters were observed between HLM and HLS9.
- Distinct expression patterns and protein-protein correlations were identified, along with sex-specific effects.
Conclusions:
- This study provides the first quantitative proteomic comparison of HLM and HLS9.
- Understanding these proteomic differences is crucial for accurate in vitro-in vivo extrapolations.
- Informed decisions regarding the choice between HLM and HLS9 for drug metabolism studies can now be made.
