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Visualization and isolation of zone-specific murine hepatocytes that maintain distinct cytochrome P450 oxidase expression in primary culture.
Metadata
Journalbiochemical and biophysical research communications2.985Date
2020 Jun 03
4 months ago
Type
Journal Article
Volume
2020-Jul-30 / 528 : 420-425
Author
Kasahara D 1, Sumiyoshi H 1, Endo H 2, Yanagawa T 1, Nakano Y 1, Matsuki Y 1, Nakao S 1, Kamiya A 3, Kimura H 4, Inagaki Y 5
Affiliation
  • 2. Department of Preventive Medicine, Tokai University School of Medicine, Isehara, Japan.
  • 3. Department of Molecular Life Sciences, Tokai University School of Medicine, Isehara, Japan.
  • 4. Department of Mechanical Engineering, Tokai University School of Engineering, Hiratsuka, Japan; Micro/Nano Technology Center, Tokai University, Hiratsuka, Japan.
  • 5. Center for Matrix Biology and Medicine, Graduate School of Medicine, Tokai University, Isehara, Japan; Department of Innovative Medical Science, Tokai University School of Medicine, Isehara, Japan; Institute of Medical Sciences, Tokai University, Isehara, Japan. Electronic address: [email protected]
Doi
PMIDMESH
Abstract
Parenchymal hepatocytes are responsible for most of the metabolic functions of the liver, but exhibit distinct functional properties depending on their localization within the hepatic lobule. Cytochrome P450 oxidases represent a family of drug-metabolizing enzymes, which are expressed predominantly in hepatocytes localized in the centrilobular area (zone 3). The present study describes a unique transgenic mouse strain that distinguishes zone 3 hepatocytes from periportal zone 1 hepatocytes by the intensity of EGFP fluorescence. Both zone 1 and zone 3 hepatocytes isolated from these mice showed the same zone-specific gene expression patterns as in liver tissue in vivo. Experiments using primary cultures of hepatocytes indicated that a combination of low oxygen concentration and activation of Wnt/β-catenin signaling maintained the expression of zone 3-specific P450 drug-metabolizing enzymes, which was characterized by their susceptibility to acetaminophen-induced mitochondrial dysfunction. These zone-specific hepatocytes provide a useful system in the research area of liver pathophysiology and drug development.
Keywords: Cytochrome P450 oxidase Drug metabolism Metabolic zonation Oxygen concentration Primary hepatocytes Wnt/β-catenin signaling
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Biochem Biophys Res Communbiochemical and biophysical research communications
Metadata
LocationUnited States
FromACADEMIC PRESS INC ELSEVIER SCIENCE

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