Down-regulation of peroxisome proliferator-activated receptor γ coactivator-1α expression in fatty acid-induced pancreatic betacell apoptosis involves nuclear factor-κB pathway
- Author:
- No author available
- Journal Title:
- Chinese Medical Journal
- Issue:
- 22
- DOI:
- 10.3760/cma.j.issn.0366-6999.2011.22.011
- Key Word:
- beta-cell;apoptosis;peroxisome proliferator-activated receptor γ coactivator-1α;nuclear factor-κB
Abstract： Background 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.Methods 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),IKBα,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.Results 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.Conclusions 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.
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