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

doi:10.1016/s0168-8278(02)00105-8

Cited by 41 publications

(28 citation statements)

References 32 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…27 Because the involvement of oxidative stress has been suggested in the pathogenesis of cellular senescence in PBC, 8,28,29 we examined the influence of oxidative stress in the expression of bmi1 and cellular senescence using cultured mBECs. We took advantage of mBECs, because nonneoplastic human BECs are not always conveniently available and the features of senescent mBECs are reportedly similar to those of senescent human BECs.…”

Section: Discussionmentioning

confidence: 99%

Decreased Expression of Bmi1 Is Closely Associated with Cellular Senescence in Small Bile Ducts in Primary Biliary Cirrhosis

Sasaki

Ikeda

Sato

et al. 2006

The American Journal of Pathology

Self Cite

View full text Add to dashboard Cite

Cellular senescence of biliary epithelial cells with p16INK4a and p21 WAF1/Cip expression in damaged small bile ducts may be critical for progressive bile duct loss in primary biliary cirrhosis. We investigated the involvement of bmi1, a polycomb group gene repressing p16INK4a expression, in the pathogenesis of biliary cellular senescence. Bmi1 expression was examined immunohistochemically in livers taken from the patients with primary biliary cirrhosis (n ‫؍‬ 18) and other diseased (n ‫؍‬ 19) and normal livers (n ‫؍‬ 16). We examined the effect of oxidative stress and a short interference RNA (siRNA) targeting bmi1 on cellular senescence in cultured mouse biliary epithelial cells. Bmi1 was widely expressed in the nuclei of biliary epithelial cells in the control livers. In contrast, bmi1 expression was significantly decreased in damaged small bile ducts in 43% of livers with primary biliary cirrhosis of stage 1/2, coordinating with the increased p16 INK4a expression. In cultured biliary epithelial cells, oxidative stress by H 2 O 2 treatment significantly decreased bmi1 expression, followed by increased P16INK4a expression. A knockdown of bmi1 induced increased p16INK4a expression, decreased cell proliferation, and increased cellular senescence. In conclusion, the decreased bmi1 expression caused by oxidative stress may be involved in the pathogenesis of cellular senescence of biliary epithelial cells in primary biliary cirrhosis.

show abstract

Section: Discussionmentioning

confidence: 99%

Decreased Expression of Bmi1 Is Closely Associated with Cellular Senescence in Small Bile Ducts in Primary Biliary Cirrhosis

Sasaki

Ikeda

Sato

et al. 2006

The American Journal of Pathology

Self Cite

View full text Add to dashboard Cite

show abstract

“…Confluent monolayers of epithelial cells were wounded as described in the "Materials and methods" section. Wound widths and images (20×) were taken before and after 24-h stimulation with and without HGF (50 ng/ml) [16,25,30]. Taken together, it is plausible that HGF, inflammatory cytokines, and oxidative stress may enhance the expression of HAI-1 in the damaged bile ducts in PBC.…”

Section: Discussionmentioning

confidence: 99%

Augmented expression of hepatocytes growth factor activator inhibitor type 1 (HAI-1) in intrahepatic small bile ducts in primary biliary cirrhosis

et al. 2006

Self Cite

View full text Add to dashboard Cite

The repair system of damaged biliary mucosa was not fully clarified so far in primary biliary cirrhosis (PBC). Given that related factors of the hepatocyte growth factor (HGF) such as HGF activator (HGFA) and HGFA inhibitor type 1 (HAI-1) participate in the repair of injured gastrointestinal mucosa, we investigated the involvement of the HGF/HGFA/HAI-1 system in PBC and control livers. The expression of HGFA, HAI-1, and c-Met was examined in PBC livers (n=24), diseased livers (control, n=30), and normal livers (n=15) by immunohistochemistry and semiquantitative reverse transcriptase-polymerase chain reaction. We examined the expression of HGFA, HAI-1, and c-Met, and the effect of HGF administration on cell proliferation and wound healing, and HAI expression in cultured mouse biliary epithelial cells (BECs). HAI-1 expression was faint in control livers, whereas it was significantly augmented in damaged small bile ducts, bile ductules, and periportal hepatocytes in PBC (p<0.05). HGFA and c-Met were homogeneously expressed in BECs in PBC and control livers. HAI-1 expression was increased at the front of wound healing and the treatment with HGF-enhanced HAI-1 expression, cell proliferation, and wound healing in cultured BECs. HGF/HGFA/HAI-1 system may participate in biliary mucosal repair as reported in gastrointestinal mucosal repair.

show abstract

“…Lipid peroxidation-producing products, including 4-hydroxynonenal, are considered important in the pathologic process leading to the bile duct damage of PBC (26). In early PBC, lipid peroxidation markers, including plasma and urinary 8-isoprostane and plasma malondialdehyde, are increased, whereas plasma antioxidants, such as total glutathione, are decreased (27).…”

Section: Discussionmentioning

confidence: 99%

Lipoprotein-X reduces LDL atherogenicity in primary biliary cirrhosis by preventing LDL oxidation

Chang

et al. 2004

Journal of Lipid Research

View full text Add to dashboard Cite

Hypercholesterolemic human LDL contains oxidized subfractions that have atherogenic properties. Paradoxically, atherosclerosis incidence is low in patients with primary biliary cirrhosis (PBC), a disease characterized by marked increases in plasma LDL, including the LDL subfraction lipoprotein-X (Lp-X). To investigate the mechanisms underlying this paradox, we first examined the propensity to oxidation of unfractionated LDL isolated from PBC patients. After prolonged incubation with copper, PBC-LDL failed to increase the oxidation index or electrophoretic mobility noted in control LDL. An admixture of PBC-LDL or Lp-X with control LDL prevented oxidation of the latter in a dose-dependent manner. PBC-LDL was also noncompetitive against copper-oxidized LDL (oxLDL) for binding with a murine monoclonal anti-oxLDL antibody in a competitive ELISA. OxLDL exerts its proapoptotic and antiangiogenic effects in part by inhibiting fibroblast growth factor 2 (FGF2) expression. Preincubation of oxLDL with PBC-LDL, but not control LDL, attenuated the inhibitory effects of oxLDL on FGF2 expression in cultured bovine aortic endothelial cells (ECs). The antioxidant and prosurvival properties of PBC-LDL diminished after the patients underwent orthotopic liver transplantation. These results suggest that Lp-X reduces LDL atherogenicity by preventing LDL oxidation to protect EC integrity in the presence of hypercholesterolemia. They also suggest that altering LDL composition may be as important as reducing LDL concentration in preventing or treating atherosclerosis. -Chang, P-Y., S-C. Lu, T-C. Su, S-F. Chou, W-H. Huang, J. D. Morrisett, C-H. Chen, C-S. Liau, and Y-T. Lee. Lipoprotein-X reduces LDL atherogenicity in primary biliary cirrhosis by preventing LDL oxidation.

show abstract

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

Cited by 41 publications

References 32 publications

Decreased Expression of Bmi1 Is Closely Associated with Cellular Senescence in Small Bile Ducts in Primary Biliary Cirrhosis

Decreased Expression of Bmi1 Is Closely Associated with Cellular Senescence in Small Bile Ducts in Primary Biliary Cirrhosis

Augmented expression of hepatocytes growth factor activator inhibitor type 1 (HAI-1) in intrahepatic small bile ducts in primary biliary cirrhosis

Lipoprotein-X reduces LDL atherogenicity in primary biliary cirrhosis by preventing LDL oxidation

Contact Info

Product

Resources

About