MEF2 activation in differentiated primary human skeletal muscle cultures requires coordinated involvement of parallel pathways
| Autor: | Lubna Al-Khalili, Mei Yu, Bertil Sjödin, Anna Krook, Alexander V. Chibalin, Juleen R. Zierath, Carolina Nylén |
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| Rok vydání: | 2004 |
| Předmět: |
Male
MAPK/ERK pathway Physiology Muscle Fibers Skeletal MAP Kinase Kinase 1 Mitogen-activated protein kinase kinase p38 Mitogen-Activated Protein Kinases Phosphatidylinositol 3-Kinases AMP-Activated Protein Kinase Kinases Insulin Myocyte Enzyme Inhibitors Cells Cultured Protein Kinase C Phosphoinositide-3 Kinase Inhibitors MEF2 Transcription Factors Cell Differentiation Middle Aged Cell biology DNA-Binding Proteins medicine.anatomical_structure Myogenic Regulatory Factors Female Mitogen-Activated Protein Kinases Signal Transduction medicine.medical_specialty p38 mitogen-activated protein kinases MADS Domain Proteins Biology Osmotic Pressure Internal medicine medicine Animals Humans Rats Wistar Muscle Skeletal Protein kinase A Protein Kinase Inhibitors Protein kinase C Mitogen-Activated Protein Kinase Kinases AMPK Skeletal muscle Cell Biology Ribonucleotides Aminoimidazole Carboxamide Rats Oxidative Stress Endocrinology Protein Kinases Transcription Factors |
| Zdroj: | American Journal of Physiology-Cell Physiology. 286:C1410-C1416 |
| ISSN: | 1522-1563 0363-6143 |
| DOI: | 10.1152/ajpcell.00444.2003 |
| Popis: | The myocyte enhancer factor (MEF)2 transcription factor is important for development of differentiated skeletal muscle. We investigated the regulation of MEF2 DNA binding in differentiated primary human skeletal muscle cells and isolated rat skeletal muscle after exposure to various stimuli. MEF2 DNA binding activity in nonstimulated (basal) muscle cultures was almost undetectable. Exposure of cells for 20 min to 120 nM insulin, 0.1 and 1.0 mM hydrogen peroxide, osmotic stress (400 mM mannitol), or 1.0 mM 5-aminoimidazole-4-carboxamide-1-beta-D-ribofuranoside (AICAR) led to a profound increase in MEF2 DNA binding. To study signaling pathways mediating MEF2 activity, we preincubated human skeletal muscle cell cultures or isolated rat epitrochlearis muscles with inhibitors of p38 mitogen-activated protein kinase (MAPK) (10 microM SB-203580), MEK1 (50 microM PD-98059), PKC (1 and 10 microM GF109203X), phosphatidylinositol (PI) 3-kinase (10 microM LY-294002), or AMP-activated protein kinase (AMPK; 20 microM compound C). All stimuli resulted primarily in activation of MEF2D DNA binding. Exposure of cells to osmotic or oxidative stress increased MEF2 DNA binding via pathways that were completely blocked by MAPK inhibitors and partially blocked by inhibitors of PKC, PI 3-kinase, and AMPK. In epitrochlearis muscle, MAPK inhibitors blocked contraction but not AICAR-mediated MEF2 DNA binding. Thus activation of MEF2 in skeletal muscle is regulated via parallel intracellular signaling pathways in response to insulin, cellular stress, or activation of AMPK. |
| Databáze: | OpenAIRE |
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