Palmitate Induces Tumor Necrosis Factor-α Expression in C2C12 Skeletal Muscle Cells by a Mechanism Involving Protein Kinase C and Nuclear Factor-κB Activation
| Autor: | Mireia Jové, Rosa M. Sánchez, Manuel Merlos, Juan C. Laguna, Anna Planavila, Manuel Vázquez-Carrera |
|---|---|
| Rok vydání: | 2006 |
| Předmět: |
medicine.medical_specialty
Pyrrolidines Palmitic Acid Naphthalenes Biology Cell Line Mice chemistry.chemical_compound Alkaloids Endocrinology Pyrrolidine dithiocarbamate Thiocarbamates Internal medicine medicine Animals Calphostin Enzyme Inhibitors Muscle Skeletal Protein kinase A Protein kinase B Protein Kinase C Protein kinase C Benzophenanthridines Tumor Necrosis Factor-alpha NF-kappa B Skeletal muscle Biological Transport Phenanthridines Glucose Chelerythrine medicine.anatomical_structure chemistry biology.protein Sesquiterpenes GLUT4 |
| Zdroj: | Endocrinology. 147:552-561 |
| ISSN: | 1945-7170 0013-7227 |
| DOI: | 10.1210/en.2005-0440 |
| Popis: | The mechanisms responsible for increased expression of TNF-alpha in skeletal muscle cells in diabetic states are not well understood. We examined the effects of the saturated acid palmitate on TNF-alpha expression. Exposure of C2C12 skeletal muscle cells to 0.75 mm palmitate enhanced mRNA (25-fold induction, P < 0.001) and protein (2.5-fold induction) expression of the proinflammatory cytokine TNF-alpha. This induction was inversely correlated with a fall in GLUT4 mRNA levels (57% reduction, P < 0.001) and glucose uptake (34% reduction, P < 0.001). PD98059 and U0126, inhibitors of the ERK-MAPK cascade, partially prevented the palmitate-induced TNF-alpha expression. Palmitate increased nuclear factor (NF)-kappaB activation and incubation of the cells with the NF-kappaB inhibitors pyrrolidine dithiocarbamate and parthenolide partially prevented TNF-alpha expression. Incubation of palmitate-treated cells with calphostin C, a strong and specific inhibitor of protein kinase C (PKC), abolished palmitate-induced TNF-alpha expression, and restored GLUT4 mRNA levels. Palmitate treatment enhanced the expression of phospho-PKCtheta, suggesting that this PKC isoform was involved in the changes reported, and coincubation of palmitate-treated cells with the PKC inhibitor chelerythrine prevented the palmitate-induced reduction in the expression of IkappaBalpha and insulin-stimulated Akt activation. These findings suggest that enhanced TNF-alpha expression and GLUT4 down-regulation caused by palmitate are mediated through the PKC activation, confirming that this enzyme may be a target for either the prevention or the treatment of fatty acid-induced insulin resistance. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|