title: NF-kappaB activation by depolarization of skeletal muscle cells depends on ryanodine and IP3 receptor-mediated calcium signals.
abstract: Depolarization of skeletal muscle cells by either high external K(+) or repetitive extracellular field potential pulses induces calcium release from internal stores. The two components of this release are mediated by either ryanodine receptors or inositol 1,4,5-trisphosphate (IP(3)) receptors and show differences in kinetics, amplitude, and subcellular localization. We have reported that the transcriptional regulators including ERKs, cAMP/Ca(2+)-response element binding protein, c-fos, c-jun, and egr-1 are activated by K(+)-induced depolarization and that their activation requires IP(3)-dependent calcium release. We presently describe the activation of the nuclear transcription factor NF-kappaB in response to depolarization by either high K(+) (chronic) or electrical pulses (fluctuating). Calcium transients of relative short duration activate an NF-kappaB reporter gene to an intermediate level, whereas long-lasting calcium increases obtained by prolonged electrical stimulation protocols of various frequencies induce maximal activation of NF-kappaB. This activation is independent of extracellular calcium, whereas calcium release mediated by either ryanodine or IP(3) receptors contribute in all conditions tested. NF-kappaB activation is mediated by IkappaBalpha degradation and p65 translocation to the nucleus. Partial blockade by N-acetyl-l-cysteine, a general antioxidant, suggests the participation of reactive oxygen species. Calcium-dependent signaling pathways such as those linked to calcineurin and PKC also contribute to NF-kappaB activation by depolarization, as assessed by blockade through pharmacological agents. These results suggest that NF-kappaB activation in skeletal muscle cells is linked to membrane depolarization and depends on the duration of elevated intracellular calcium. It can be regulated by sequential activation of calcium release mediated by the ryanodine and by IP(3) receptors.
authors.affiliation: Centro Fondo Nacional de Investigación en Areas Prioritarias de Estudios Moleculares de la Célula, Facultad de Medicina, Universidad de Chile, Santiago, Chile.
authors.forename: Juan Antonio
authors.initials: JA
authors.lastname: Valdés
authors.forename: Jorge
authors.initials: J
authors.lastname: Hidalgo
authors.forename: José Luis
authors.initials: JL
authors.lastname: Galaz
authors.forename: Natalia
authors.initials: N
authors.lastname: Puentes
authors.forename: Mónica
authors.initials: M
authors.lastname: Silva
authors.forename: Enrique
authors.initials: E
authors.lastname: Jaimovich
authors.forename: M Angélica
authors.initials: MA
authors.lastname: Carrasco
mesh_terms: D021581:Active Transport, Cell Nucleus; D000818:Animals; D000831:Animals, Newborn; D019703:Calcineurin / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D020013:Calcium Signaling; D002460:Cell Line; D004558:Electric Stimulation; D020672:I-kappa B Proteins / Q000378:metabolism; D053496:Inositol 1,4,5-Trisphosphate Receptors / Q000378:metabolism*; D007700:Kinetics; D008564:Membrane Potentials; D051379:Mice; D018485:Muscle Fibers, Skeletal / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000166:cytology / Q000378:metabolism*; D032448:Myoblasts, Skeletal / Q000378:metabolism*; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism*; D011188:Potassium / Q000378:metabolism; D011401:Promoter Regions, Genetic; D011493:Protein Kinase C / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D019837:Ryanodine Receptor Calcium Release Channel / Q000378:metabolism*; D051996:Transcription Factor RelA / Q000378:metabolism; D014158:Transcription, Genetic
chemical_list: D020672:I-kappa B Proteins; D053496:Inositol 1,4,5-Trisphosphate Receptors; D016328:NF-kappa B; C000606205:Nfkbia protein, mouse; C000606206:Nfkbia protein, rat; D017382:Reactive Oxygen Species; D019837:Ryanodine Receptor Calcium Release Channel; D051996:Transcription Factor RelA; D000072000:NF-KappaB Inhibitor alpha; D011493:Protein Kinase C; D019703:Calcineurin; D011188:Potassium; D002118:Calcium