Nitric oxide facilitates NFAT-dependent transcription in mouse myotubes
| Autor: | Catherine G. Simmons, David S. Criswell, Jeff E. Sellman, Vitor A. Lira, Jason A. Drenning, Quinlyn A. Soltow |
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| Rok vydání: | 2008 |
| Předmět: |
Physiology
Muscle Fibers Skeletal Biology Nitric Oxide Calcium in biology Cell Line Nitric oxide Glycogen Synthase Kinase 3 Mice chemistry.chemical_compound medicine Animals RNA Messenger Phosphorylation Calcimycin Glycogen Synthase Kinase 3 beta Ionophores Myosin Heavy Chains NFATC Transcription Factors Myogenesis Effector Skeletal muscle NFAT Cell Biology Molecular biology Cell biology Calcineurin Nitric oxide synthase NG-Nitroarginine Methyl Ester medicine.anatomical_structure Gene Expression Regulation chemistry Guanylate Cyclase biology.protein Calcium Nitric Oxide Synthase Triazenes |
| Zdroj: | American Journal of Physiology-Cell Physiology. 294:C1088-C1095 |
| ISSN: | 1522-1563 0363-6143 |
| Popis: | Intracellular calcium transients in skeletal muscle cells initiate phenotypic adaptations via activation of calcineurin and its effector nuclear factor of activated t-cells (NFAT). Furthermore, endogenous production of nitric oxide (NO) via calcium-calmodulin-dependent NO synthase (NOS) is involved in skeletal muscle phenotypic plasticity. Here, we provide evidence that NO enhances calcium-dependent nuclear accumulation and transcriptional activity of NFAT and induces phosphorylation of glycogen synthase kinase-3beta (GSK-3beta) in C2C12 myotubes. The calcium ionophore A23187 (1 microM for 9 h) or thapsigargin (2 microM for 4 h) increased NFAT transcriptional activity by seven- and fourfold, respectively, in myotubes transiently transfected with an NFAT-dependent reporter plasmid (pNFAT-luc, Stratagene). Cotreatment with the NOS-inhibitor N(G)-nitro-L-arginine methyl ester (L-NAME; 5 mM) or the guanylate cyclase inhibitor 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ; 10 microM) prevented the calcium effects on NFAT activity. The NO donor diethylenetriamine-NONO (DETA-NO; 10 microM) augmented the effects of A23187 on NFAT-dependent transcription. Similarly, A23187 (0.4 microM for 4 h) caused nuclear accumulation of NFAT and increased phosphorylation (i.e., inactivation) of GSK-3beta, whereas cotreatment with L-NAME or ODQ inhibited these responses. Finally, the NO donor 3-(2-hydroxy-2-nitroso-1-propylhydrazino)-1-propanamine (PAPA-NO; 1 microM for 1 h) increased phosphorylation of GSK-3beta in a manner dependent on guanylate cyclase activity. We conclude that NOS activity mediates calcium-induced phosphorylation of GSK-3beta and activation of NFAT-dependent transcription in myotubes. Furthermore, these effects of NO are guanylate cyclase-dependent. |
| Databáze: | OpenAIRE |
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