Damaged interlobular bile ducts in primary biliary cirrhosis show reduced expression of glutathione-S-transferase-pi and aberrant expression of 4-hydroxynonenal

Koichi Tsuneyama, Kenichi Harada, Naoko Kono, Motoko Sasaki, Takahito Saito, M. Eric Gershwin, Mamoru Ikemoto, Hiroyuki Arai, Yasuni Nakanuma

Research output: Contribution to journalArticle

34 Scopus citations

Abstract

Background/Aims: Chronic inflammation induces oxidative stress by producing reactive oxygen species. We investigated how the oxidative stress associated with chronic cholangitis induce bile duct damages in primary biliary cirrhosis. Methods: The intracellular status of lipid peroxidation due to oxidative stress and that of glutathione, an endogenous cytoprotective molecule, were examined in primary biliary cirrhosis and controls by immunostaining of 4-hydroxynonenal and glutathione-S-transferase-pi. The former is a by-product of lipid peroxidation, and the latter is involved in the formation of intracellular glutathione. Results: In the damaged bile ducts of primary biliary cirrhosis, glutathione-S-transferase-pi expression was markedly reduced, reflecting reduction of intracellular glutathione, and perinuclear expression of 4-hydroxynonenal was frequent, reflecting active lipid peroxidation associated with biliary epithelial damages. There was diffuse/luminal expression of 4-hydroxynonenal in the bile ducts frequent in primary biliary cirrhosis and controls, likely reflecting absorption of 4-hydroxynonenal, also a component of oxidized low-density lipoprotein, from bile via scavenger receptor class B type 1 on biliary epithelium. Conclusions: The data suggest that lipid peroxidation in the bile ducts with reduced expression of glutathione-S-transferase-pi, may be an important pathologic process leading to the bile duct damage of primary biliary cirrhosis.

Original languageEnglish (US)
Pages (from-to)176-183
Number of pages8
JournalJournal of Hepatology
Volume37
Issue number2
DOIs
StatePublished - 2002

Keywords

  • 4-Hydroxynonenal
  • Interlobular bile duct
  • Lipid peroxidation
  • Primary biliary cirrhosis
  • Scavenger receptor class B type 1

ASJC Scopus subject areas

  • Gastroenterology

Fingerprint Dive into the research topics of 'Damaged interlobular bile ducts in primary biliary cirrhosis show reduced expression of glutathione-S-transferase-pi and aberrant expression of 4-hydroxynonenal'. Together they form a unique fingerprint.

  • Cite this