PGC-1α is downregulated in a mouse model of obstructive cholestasis but not in a model of liver fibrosis.
FEBS Open Bio
; 11(1): 61-74, 2021 01.
Article
em En
| MEDLINE
| ID: mdl-32860664
ABSTRACT
Several studies have indicated that cholestatic liver damage involves mitochondria dysfunction. However, the precise mechanism by which hydrophobic bile salts cause mitochondrial dysfunction is not clear. In this study, we intended to determine the pathogenesis of cholestatic liver injury associated with peroxisome proliferator-activated receptor-γ co-activator 1α (PGC-1α). A mouse model of cholestatic liver disease was generated by surgical ligation of the bile duct (BDL), and a mouse model of fibrosis was developed through serial administration of thioacetamide. After obtaining liver specimens on scheduled days, we compared the expression of the antioxidant enzymes (superoxide dismutase 2 [SOD2], catalase, and glutathione peroxidase-1[GPx-1]) and PGC-1α in livers from mice with fibrosis and cholestasis using western blotting, immunohistochemistry, and immunofluorescence. We found that cholestatic livers exhibit lower expression of antioxidant enzymes, such as SOD2, catalase, and PGC-1α. In contrast, fibrotic livers exhibit higher expression of antioxidant enzymes and PGC-1α. In addition, cholestatic livers exhibited significantly lower expression of pro-apoptotic markers (Bax) as compared to fibrotic livers. It is well known that overexpression of PGC-1α increases mitochondrial antioxidant enzyme expression, and vice versa. Thus, we concluded that obstructive cholestasis decreases expression of PGC-1α, which may lead to decreased expression of mitochondrial antioxidant enzymes, thereby rendering mice with cholestatic livers vulnerable to ROS-induced cell death.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Colestase
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Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo
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Fígado
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Cirrose Hepática Experimental
Tipo de estudo:
Etiology_studies
Limite:
Animals
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Humans
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Male
Idioma:
En
Revista:
FEBS Open Bio
Ano de publicação:
2021
Tipo de documento:
Article
País de publicação:
ENGLAND
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ESCOCIA
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GB
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GREAT BRITAIN
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INGLATERRA
/
REINO UNIDO
/
SCOTLAND
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UK
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UNITED KINGDOM