Fatty liver and anti-oxidant enzyme activities along with peroxisome proliferator-activated receptors γ and α expressions in the liver of Wilson's disease.

Abstract

BACKGROUND:

The mechanisms of liver damage and steatosis in Wilson's disease (WD) presenting accumulation of copper generating oxidants remain unclear. Recent studies have shown that peroxisome proliferator-activated receptors (PPARs), in particular PPARs α and γ, regulate fat content of the liver together with the anti-oxidant and anti-inflammation systems. However, such PPARs have never been studied in WD.

METHODS:

We examined PPARs along with the liver damage and steatosis of WD using liver specimens from affected patients exhibiting mild liver damage (group I, n = 5), moderate or greater liver damage (group II, n = 10) and fulminant hepatic failure (group III, n = 5), and from asymptomatic carriers (group H, n = 4).

RESULTS:

PPAR α expression was increased over the control levels in groups H and I but was decreased in groups II and III in parallel with the progression of liver damage (group H = I>II>III). PPAR γ expression was inversely increased (group H<I<II<III). Mn-dependent superoxide dismutase (Mn-SOD), CuZn-SOD, and catalase activities were decreased in the affected three groups, and were increased in group H. Among group II exhibiting substantial inter-individual variances in parameters, the severity of steatosis showed a significant positive correlation with PPAR γ expression (p<0.001) but not PPAR α expression. CuZn-SOD activity was positively correlated with PPARα expression (p<0.05) but not PPAR γ expression.

CONCLUSION:

These results suggest that changes of PPARs γ and α are associated with the steatosis and the impairment of anti-oxidant system in the liver of WD.

• Authors: Hironori Nagasaka, Takashi Miida, Ayano Inui, Ikuo Inoue, Hirokazu Tsukahara, Haruki Komatsu, Eitaro Hiejima, Tomoo Fujisawa, Tohru Yorifuji, Ken-ichi Hiranao, Hideaki Okajima, Yukihiro Inomata
• Journal: Molecular genetics and metabolism (Mol Genet Metab) Vol. 107 Issue 3 Pg. 542-7 (Nov 2012) ISSN: 1096-7206 [Electronic] United States
• PMID: 22940187 (Publication Type: Journal Article)
• Copyright: Copyright © 2012 Elsevier Inc. All rights reserved.

Chemical References

• Cation Transport Proteins
• Isoenzymes
• PPAR alpha
• PPAR gamma
• Copper
• Catalase
• Superoxide Dismutase
• Adenosine Triphosphatases
• Copper-Transporting ATPases

Topics

• Adenosine Triphosphatases (genetics)
• Adolescent
• Adult
• Asymptomatic Diseases
• Catalase (metabolism)
• Cation Transport Proteins (genetics)
• Child
• Child, Preschool
• Copper (metabolism)
• Copper-Transporting ATPases
• Fatty Liver (genetics, metabolism, pathology)
• Female
• Gene Expression
• Hepatolenticular Degeneration (genetics, metabolism, pathology)
• Humans
• Isoenzymes (metabolism)
• Liver (metabolism, pathology)
• Male
• Mutation
• PPAR alpha (genetics, metabolism)
• PPAR gamma (genetics, metabolism)
• Severity of Illness Index
• Superoxide Dismutase (metabolism)