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 language | English (US) |
|---|---|
| Pages (from-to) | 176-183 |
| Number of pages | 8 |
| Journal | Journal of Hepatology |
| Volume | 37 |
| Issue number | 2 |
| DOIs | |
| State | Published - 2002 |
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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 journal › Article
}
TY - JOUR
T1 - Damaged interlobular bile ducts in primary biliary cirrhosis show reduced expression of glutathione-S-transferase-pi and aberrant expression of 4-hydroxynonenal
AU - Tsuneyama, Koichi
AU - Harada, Kenichi
AU - Kono, Naoko
AU - Sasaki, Motoko
AU - Saito, Takahito
AU - Gershwin, M. Eric
AU - Ikemoto, Mamoru
AU - Arai, Hiroyuki
AU - Nakanuma, Yasuni
PY - 2002
Y1 - 2002
N2 - 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.
AB - 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.
KW - 4-Hydroxynonenal
KW - Interlobular bile duct
KW - Lipid peroxidation
KW - Primary biliary cirrhosis
KW - Scavenger receptor class B type 1
UR - http://www.scopus.com/inward/record.url?scp=0036022847&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0036022847&partnerID=8YFLogxK
U2 - 10.1016/S0168-8278(02)00105-8
DO - 10.1016/S0168-8278(02)00105-8
M3 - Article
C2 - 12127421
AN - SCOPUS:0036022847
VL - 37
SP - 176
EP - 183
JO - Journal of Hepatology
JF - Journal of Hepatology
SN - 0168-8278
IS - 2
ER -