title: Visualizing and quantifying difference in cytoplasmic and nuclear metabolism in the hepatobiliary system in vivo.
abstract: The liver is a major organ responsible for performing xenobiotic metabolism. In this process, xenobiotic is uptaken and processed in hepatocytes and subsequently excreted into the bile canaliculi. However, the intracellular heterogeneity in such metabolic processes is not known. We use the molecular probe 6-carboxyfluorescein diacetate (6-CFDA) to investigate xenobiotic metabolism in hepatocytes with intravital multiphoton fluorescence microscopy. 6-CFDA is processed by intracellular esterase to fluorescent 6-CF, which can be imaged and quantified. We found that compared to the nucleus, cytoplasmic 6-CF fluorescence intensity reached a maximum earlier (cytoplasm: 11.3 ± 4.4 min; nucleus: 14.7 ± 4.9 min) following 6-CFDA injection. We also found a slight difference in the rate of 6-CFDA metabolism as the rates of 6-CF decay at rates of 1.43 ± 0.75 and 1.27 ± 0.72 photons/min for the cytoplasm and nucleus, respectively. These results indicate that molecular transport to the nucleus is additionally hindered and can affect drug transport there
authors.affiliation: National Taiwan University, Department of Physics, Taipei 106, Taiwan.
authors.forename: Chih-Ju
authors.initials: CJ
authors.lastname: Lin
authors.affiliation: National Taiwan University, Department of Physics, Taipei 106, Taiwan.
authors.forename: Ning
authors.initials: N
authors.lastname: Kang
authors.affiliation: National Taiwan University, Department of Physics, Taipei 106, Taiwan.
authors.forename: Jian-Ye
authors.initials: JY
authors.lastname: Lee
authors.affiliation: National Taiwan University Hospital and National Taiwan University, College of Medicine, Department of Internal Medicine, Taipei 100, TaiwancNational Taiwan University, Institute of Biotechnology, Taipei 106, Taiwan.
authors.forename: Hsuan-Shu
authors.initials: HS
authors.lastname: Lee
authors.affiliation: National Taiwan University, Department of Physics, Taipei 106, TaiwandNational Taiwan University, Center for Optoelectronic Biomedicine, Taipei 106, TaiwaneNational Taiwan University, Center for Quantum Science and Engineering, Taipei 106, Taiwan.
authors.forename: Chen-Yuan
authors.initials: CY
authors.lastname: Dong
mesh_terms: D000818:Animals; D001659:Biliary Tract / Q000737:chemistry / Q000166:cytology / Q000378:metabolism*; D002467:Cell Nucleus / Q000737:chemistry / Q000378:metabolism*; D003593:Cytoplasm / Q000737:chemistry / Q000378:metabolism*; D005452:Fluoresceins; D005456:Fluorescent Dyes; D022781:Hepatocytes / Q000737:chemistry / Q000378:metabolism; D008099:Liver / Q000737:chemistry / Q000166:cytology / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D036641:Microscopy, Fluorescence, Multiphoton / Q000379:methods*; D059008:Time-Lapse Imaging / Q000379:methods
chemical_list: D005452:Fluoresceins; D005456:Fluorescent Dyes; C093616:6-carboxyfluorescein diacetate