title: Hepatic expression of gamma-glutamyltranspeptidase in the human liver of patients with alcoholic liver disease.
abstract: BACKGROUND
  Gamma-glutamyltranspeptidase (GGT) has been recognized as an enzyme that converts glutathione into cysteine, and it is localized predominantly within the liver. Serum GGT is clinically recognized as the most useful marker for diagnosis of alcoholic liver disease (ALD).
  
  
  METHODS
  GGT localization within the liver was examined immunohistochemically using an anti-GGT antibody and was visualized by confocal laser scanning microscopy in ALD and normal livers. Double immunostaining for GGT and dipeptidylpeptidase-IV (DPP-IV) was carried out to evaluate GGT localization in greater detail.
  
  
  RESULTS
  Expression of GGT protein and mRNA was studied with immunoblot analysis and in situ hybridization, respectively. Immunohistochemically, the expression of GGT in the normal liver was faintly demonstrated in the bile canaliculi of hepatocytes and in biliary epithelial cells. In ALD livers, GGT was clearly demonstrated at the same sites. Double immunostaining demonstrated that GGT and DPP-IV were colocalized in hepatocytes in the ALD liver. In situ hybridization clearly demonstrated GGT-mRNA within the cytoplasm of hepatocytes and biliary epithelial cells. Immunoblot analysis revealed that GGT protein expression was increased in the ALD livers compared with that seen in the normal livers.
  
  
  CONCLUSIONS
  These findings indicate that GGT in control and alcoholic livers is synthesized in hepatocytes and biliary epithelial cells, and is localized within the bile canalicular membrane and the luminal membrane in those cells, respectively. In conclusion, GGT synthesis and protein expression are increased in ALD livers, leading to the elevation of serum levels of GGT that are commonly noted in patients with the disease.
authors.affiliation: Third Department of Medicine, Fukuoka University School of Medicine, Fukuoka, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Irie
authors.forename: Norihisa
authors.initials: N
authors.lastname: Suzuki
authors.forename: Tetsuro
authors.initials: T
authors.lastname: Sohda
authors.forename: Akira
authors.initials: A
authors.lastname: Anan
authors.forename: Kaoru
authors.initials: K
authors.lastname: Iwata
authors.forename: Yasuaki
authors.initials: Y
authors.lastname: Takeyama
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Watanabe
authors.forename: Peter
authors.initials: P
authors.lastname: Fischer
authors.forename: Jürgen E
authors.initials: JE
authors.lastname: Scherberich
authors.forename: Shotaro
authors.initials: S
authors.lastname: Sakisaka