PloS one, 2012, Vol.7 (1), p.e29985-e29985
2012
Volltextzugriff (PDF)
Details
- Autor(en) / Beteiligte
- Titel
- PGC-1α induces mitochondrial and myokine transcriptional programs and lipid droplet and glycogen accumulation in cultured human skeletal muscle cells
- Ist Teil von
- PloS one, 2012, Vol.7 (1), p.e29985-e29985
- Ort / Verlag
- United States: Public Library of Science
- Erscheinungsjahr
- 2012
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- The transcriptional coactivator peroxisome proliferator-activated receptor-gamma coactivator 1 alpha (PGC-1α) is a chief activator of mitochondrial and metabolic programs and protects against atrophy in skeletal muscle (skm). Here we tested whether PGC-1α overexpression could restructure the transcriptome and metabolism of primary cultured human skm cells, which display a phenotype that resembles the atrophic phenotype. An oligonucleotide microarray analysis was used to reveal the effects of PGC-1α on the whole transcriptome. Fifty-three different genes showed altered expression in response to PGC-1α: 42 upregulated and 11 downregulated. The main gene ontologies (GO) associated with the upregulated genes were mitochondrial components and processes and this was linked with an increase in COX activity, an indicator of mitochondrial content. Furthermore, PGC-1α enhanced mitochondrial oxidation of palmitate and lactate to CO(2), but not glucose oxidation. The other most significantly associated GOs for the upregulated genes were chemotaxis and cytokine activity, and several cytokines, including IL-8/CXCL8, CXCL6, CCL5 and CCL8, were within the most highly induced genes. Indeed, PGC-1α highly increased IL-8 cell protein content. The most upregulated gene was PVALB, which is related to calcium signaling. Potential metabolic regulators of fatty acid and glucose storage were among mainly regulated genes. The mRNA and protein level of FITM1/FIT1, which enhances the formation of lipid droplets, was raised by PGC-1α, while in oleate-incubated cells PGC-1α increased the number of smaller lipid droplets and modestly triglyceride levels, compared to controls. CALM1, the calcium-modulated δ subunit of phosphorylase kinase, was downregulated by PGC-1α, while glycogen phosphorylase was inactivated and glycogen storage was increased by PGC-1α. In conclusion, of the metabolic transcriptome deficiencies of cultured skm cells, PGC-1α rescued the expression of genes encoding mitochondrial proteins and FITM1. Several myokine genes, including IL-8 and CCL5, which are known to be constitutively expressed in human skm cells, were induced by PGC-1α.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 1932-6203eISSN: 1932-6203DOI: 10.1371/journal.pone.0029985Titel-ID: cdi_plos_journals_1323077868
- Format
- –
- Schlagworte
- Atrophy, Bayesian analysis, Bioaccumulation, Bioinformatics, Biology, Biomedical research, Biosynthesis, Blotting, Western, Calcium, Calcium signalling, Calmodulin - genetics, Calmodulin - metabolism, Carbon dioxide, Cells, Cultured, Chemokine CCL5 - genetics, Chemokine CCL5 - metabolism, Chemokine CCL8 - genetics, Chemokine CCL8 - metabolism, Chemokine CXCL6 - genetics, Chemokine CXCL6 - metabolism, Chemotaxis, Cytokines, Cytokines - genetics, Cytokines - metabolism, Diabetes, Disorders of metabolism, DNA microarrays, Droplets, Electron Transport Complex IV - genetics, Electron Transport Complex IV - metabolism, Fasting, Fatty acids, Fisiologia patològica, Gene expression, Genes, Genomes, Genètica molecular, Glucose, Glycogen, Glycogen - metabolism, Glycogen phosphorylase, Heat-Shock Proteins - genetics, Heat-Shock Proteins - metabolism, Humans, Interleukin 8, Interleukin-8 - genetics, Interleukin-8 - metabolism, Laboratories, Lactic acid, Lipids, Lipids - analysis, Membrane Proteins - genetics, Membrane Proteins - metabolism, Metabolism, Mitochondria, Mitochondrial Proteins - genetics, Mitochondrial Proteins - metabolism, Molecular genetics, Muscle Cells - cytology, Muscle Cells - metabolism, Muscle, Skeletal - cytology, Muscle, Skeletal - metabolism, Muscles, Musculoskeletal system, Oligonucleotide Array Sequence Analysis, Oligonucleotides, Oxidation, Palmitic acid, Parvalbumins - genetics, Parvalbumins - metabolism, Pathological physiology, Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha, Phosphorylase, Phosphorylase kinase, Phosphorylation, Primary Cell Culture, Proteins, Regulators, Reverse Transcriptase Polymerase Chain Reaction, Rodents, Skeletal muscle, Storage, Trans-Activators - genetics, Trans-Activators - metabolism, Transcription, Transcription Factors - genetics, Transcription Factors - metabolism, Transcriptome, Transgenic animals, Trastorns del metabolisme, Triglycerides, Triglycerides - metabolism