Regulation of hepatic cardiolipin metabolism by TNFα: Implication in cancer cachexia.
Biochim Biophys Acta
; 1851(11): 1490-500, 2015 Nov.
Article
em En
| MEDLINE
| ID: mdl-26327596
ABSTRACT
Cardiolipin (CL) content accumulation leads to an increase in energy wasting in liver mitochondria in a rat model of cancer cachexia in which tumor necrosis factor alpha (TNFα) is highly expressed. In this study we investigated the mechanisms involved in liver mitochondria CL accumulation in cancer cachexia and examined if TNFα was involved in this process leading to mitochondrial bioenergetics alterations. We studied gene, protein expression and activity of the main enzymes involved in CL metabolism in liver mitochondria from a rat model of cancer cachexia and in HepaRG hepatocyte-like cells exposed to 20 ng/ml of TNFα for 12 h. Phosphatidylglycerolphosphate synthase (PGPS) gene expression was increased 2.3-fold (p<0.02) and cardiolipin synthase (CLS) activity decreased 44% (p<0.03) in cachectic rat livers compared to controls. CL remodeling enzymes monolysocardiolipin acyltransferase (MLCL AT-1) activity and tafazzin (TAZ) gene expression were increased 30% (p<0.01) and 50% (p<0.02), respectively, in cachectic rat livers compared to controls. Incubation of hepatocytes with TNFα increased CL content 15% (p<0.05), mitochondrial oxygen consumption 33% (p<0.05), PGPS gene expression 44% (p<0.05) and MLCL AT-1 activity 20% (p<0.05) compared to controls. These above findings strongly suggest that in cancer cachexia, TNFα induces a higher energy wasting in liver mitochondria by increasing CL content via upregulation of PGPS expression.
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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Neoplasias Peritoneais
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Caquexia
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Cardiolipinas
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Regulação Neoplásica da Expressão Gênica
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Fator de Necrose Tumoral alfa
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Hepatócitos
Tipo de estudo:
Prognostic_studies
Limite:
Animals
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Humans
Idioma:
En
Revista:
Biochim Biophys Acta
Ano de publicação:
2015
Tipo de documento:
Article