Saturated free fatty acid sodium palmitate-induced lipoapoptosis by targeting glycogen synthase kinase-3ß activation in human liver cells.
Dig Dis Sci
; 59(2): 346-57, 2014 Feb.
Article
en En
| MEDLINE
| ID: mdl-24132507
ABSTRACT
BACKGROUND:
Elevated serum saturated fatty acid levels and hepatocyte lipoapoptosis are features of nonalcoholic fatty liver disease (NAFLD).AIM:
The purpose of this study was to investigate saturated fatty acid induction of lipoapoptosis in human liver cells and the underlying mechanisms.METHODS:
Human liver L02 and HepG2 cells were treated with sodium palmitate, a saturated fatty acid, for up to 48 h with or without lithium chloride, a glycogen synthase kinase-3ß (GSK-3ß) inhibitor, or GSK-3ß shRNA transfection. Transmission electron microscopy was used to detect morphological changes, flow cytometry was used to detect apoptosis, a colorimetric assay was used to detect caspase-3 activity, and western blot analysis was used to detect protein expression.RESULTS:
The data showed that sodium palmitate was able to induce lipoapoptosis in L02 and HepG2 cells. Western blot analysis showed that sodium palmitate activated GSK-3ß protein, which was indicated by dephosphorylation of GSK-3ß at Ser-9. However, inhibition of GSK-3ß activity with lithium chloride treatment or knockdown of GSK-3ß expression with shRNA suppressed sodium palmitate-induced lipoapoptosis in L02 and HepG2 cells. On a molecular level, inhibition of GSK-3ß expression or activity suppressed sodium palmitate-induced c-Jun-N-terminal kinase (JNK) phosphorylation and Bax upregulation, whereas GSK-3ß inhibition did not affect endoplasmic reticulum stress-induced activation of unfolded protein response.CONCLUSIONS:
The present data demonstrated that saturated fatty acid sodium palmitate-induced lipoapoptosis in human liver L02 and HepG2 cells was regulated by GSK-3ß activation, which led to JNK activation and Bax upregulation. This finding indicates that GSK-3ß inhibition may be a potential therapeutic target to control NAFLD.
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Apoptosis
/
Ácido Palmítico
/
Hepatocitos
/
Glucógeno Sintasa Quinasa 3
/
Hígado Graso
/
Hígado
Límite:
Humans
Idioma:
En
Revista:
Dig Dis Sci
Año:
2014
Tipo del documento:
Article