Down-regulation of peroxisome proliferator-activated receptor γ coactivator-1α expression in fatty acid-induced pancreatic beta-cell apoptosis involves nuclear factor-κB pathway / 中华医学杂志(英文版)
Chinese Medical Journal
; (24): 3657-3663, 2011.
Article
en En
| WPRIM
| ID: wpr-273996
Biblioteca responsable:
WPRO
ABSTRACT
<p><b>BACKGROUND</b>Pancreatic beta-cell apoptosis induced by lipotoxicity, to a large extent, contributes to the progression of type 2 diabetes. To investigate the mechanism of free fatty acid induced apoptosis, we aimed to study the effects of palmitic acid (PA) on the apoptosis and peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α) expression in βTC3 cells as well as the possible role of nuclear factor-κB (NF-κB) in this process.</p><p><b>METHODS</b>Hoechst 33258 was used to detect βTC3 cell apoptosis, which was induced by PA stimulation for 12 hours. PGC-1α expression was analyzed by reverse transcription polymerase chain reaction, IκB kinase β (IKKβ), IκBα, NF-κB-inducing kinase (NIK) and Rel-B expressions were analyzed by Western blotting. MG132 was employed to block the endogenous IκBα degradation before PA administration, and then its effect on PA-inducing cell apoptosis and PGC-1α mRNA expression was analyzed.</p><p><b>RESULTS</b>Significant increased cell apoptosis was found at the concentration of 0.5 mmol/L and 1.0 mmol/L PA administration. PA (0.5 mmol/L) could extensively reduced the expression of PGC-1α mRNA. After exposing βTC3 cells to 0.5 mmol/L PA for different time periods (0, 4, 6, 8, 10 and 12 hours), IKKβ protein expression increased while IκBα, NIK and Rel-B protein expression declined in a time-dependent manner. Pretreatment with MG132 to inhibit the degradation of IκBα, partially prevented the down-regulation of PGC-1α mRNA expression after 12-hour PA treatment in accordance with the decrease of PA induced apoptosis.</p><p><b>CONCLUSIONS</b>NF-κB canonical pathway was activated in PA-mediated βTC3 cell apoptosis, whereas non-canonical pathway was inhibited. Reduced PGC-1α expression by PA in βTC3 cells could involve the activation of canonical NF-κB pathway, so as to deteriorate the PA induced apoptosis.</p>
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Base de datos:
WPRIM
Asunto principal:
Farmacología
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Factores de Transcripción
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Transducción de Señal
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Línea Celular
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FN-kappa B
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Apoptosis
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Ácido Palmítico
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Reacción en Cadena de la Polimerasa de Transcriptasa Inversa
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Células Secretoras de Insulina
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Coactivador 1-alfa del Receptor Activado por Proliferadores de Peroxisomas gamma
Límite:
Humans
Idioma:
En
Revista:
Chinese Medical Journal
Año:
2011
Tipo del documento:
Article