Document Detail


Drug metabolite heterogeneity in cultured single cells profiled by pico-trapping direct mass spectrometry.
MedLine Citation:
PMID:  22583577     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Aim: We investigated the heterogeneity of tafluprost metabolism in primary human hepatocytes at a single-cell level by live single-cell mass spectrometry (MS). Materials & methods: Picoliter volumes of cytoplasm were analyzed by nano-electrospray ionization MS in order to obtain single-cell metabolite profiles. The subcellular components of a single tafluprost-treated human hepatocyte were isolated and the single-cell metabolite profile was compared with those of traditional bulk hepatocyte analysis. Results: In the bulk hepatocyte analysis, liquid chromatography-MS showed the averaged metabolism of tafluprost to tafluprost acid (TA) and β-oxidized metabolites. However, live single-cell MS showed that tafluprost metabolism varied among individual cells. In addition, there was significant variation in the quantities of TA and a major metabolite, dinor-TA, among cells, whereas there was no significant variation in 7-ethoxycoumarin metabolism. Conclusion: Thus, live single-cell MS successfully detected the heterogeneity of drug metabolism in individual living hepatocytes. Original submitted 12 May 2011; Revised submitted 6 February 2012.
Authors:
Yasufumi Fukano; Naohiro Tsuyama; Hajime Mizuno; Sachiko Date; Mikihisa Takano; Tsutomu Masujima
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-5-14
Journal Detail:
Title:  Nanomedicine (London, England)     Volume:  -     ISSN:  1748-6963     ISO Abbreviation:  -     Publication Date:  2012 May 
Date Detail:
Created Date:  2012-5-15     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101278111     Medline TA:  Nanomedicine (Lond)     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
Graduate School of Biomedical Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8551, Japan.
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