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

33 Citations (Scopus)

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

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Glutathione S-Transferase pi
Biliary Liver Cirrhosis
Bile Ducts
Glutathione
Lipid Peroxidation
Oxidative Stress
CD36 Antigens
Cholangitis
Pathologic Processes
Bile
Reactive Oxygen Species
Epithelium
4-hydroxy-2-nonenal
Inflammation

Keywords

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

ASJC Scopus subject areas

  • Gastroenterology

Cite this

Damaged interlobular bile ducts in primary biliary cirrhosis show reduced expression of glutathione-S-transferase-pi and aberrant expression of 4-hydroxynonenal. / Tsuneyama, Koichi; Harada, Kenichi; Kono, Naoko; Sasaki, Motoko; Saito, Takahito; Gershwin, M. Eric; Ikemoto, Mamoru; Arai, Hiroyuki; Nakanuma, Yasuni.

In: Journal of Hepatology, Vol. 37, No. 2, 2002, p. 176-183.

Research output: Contribution to journalArticle

Tsuneyama, Koichi ; Harada, Kenichi ; Kono, Naoko ; Sasaki, Motoko ; Saito, Takahito ; Gershwin, M. Eric ; Ikemoto, Mamoru ; Arai, Hiroyuki ; Nakanuma, Yasuni. / Damaged interlobular bile ducts in primary biliary cirrhosis show reduced expression of glutathione-S-transferase-pi and aberrant expression of 4-hydroxynonenal. In: Journal of Hepatology. 2002 ; Vol. 37, No. 2. pp. 176-183.
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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.",
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AU - Sasaki, Motoko

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