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This Article Full Text Full Text (PDF) All Versions of this Article: 106/4/1301    most recent 91224.2008v1 Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Osorio-Fuentealba, C. Articles by Carrasco, M. A. Search for Related Content PubMed PubMed Citation Articles by Osorio-Fuentealba, C. Articles by Carrasco, M. A.

Hypoxia stimulates via separate pathways ERK phosphorylation and NF-B activation in skeletal muscle cells in primary culture

¹Centro Fondo Nacional de Investigación en Áreas Prioritarias de Estudios Moleculares de la Célula, Facultad de Medicina, Universidad de Chile; ²Programa de Fisiología y Biofísica and ³Programa de Biología Celular y Molecular, Instituto de Ciencias Biomédicas, Facultad de Medicina, Universidad de Chile; and ⁴Departamento de Ciencias Biológicas, Facultad de Ecología y Recursos Naturales, Universidad Andres Bello, Santiago, Chile

Submitted 12 September 2008 ; accepted in final form 28 January 2009

Mammalian cells sense oxygen levels and respond to hypoxic conditions through the regulation of multiple signaling pathways and transcription factors. Here, we investigated the effects of hypoxia on the activity of two transcriptional regulators, ERK1/2 and NF-B, in skeletal muscle cells in primary culture. We found that hypoxia significantly enhanced ERK1/2 phosphorylation and that it stimulated NF-B-dependent gene transcription as well as nuclear translocation of a green fluorescent protein-labeled p65 NF-B isoform. Phosphorylation of ERK1/2- and NF-B-dependent transcription by hypoxia required calcium entry through L-type calcium channels. Calcium release from ryanodine-sensitive stores was also necessary for ERK1/2 activation but not for NF-B-dependent-transcription. N-acetylcysteine, a general scavenger of reactive oxygen species, blocked hypoxia-induced ROS generation but did not affect the stimulation of ERK1/2 phosphorylation induced by hypoxia. In contrast, NF-B activation was significantly inhibited by N-acetylcysteine and did not depend on ERK1/2 stimulation, as shown by the lack of effect of the upstream ERK inhibitor U-0126. These separate pathways of activation of ERK1/2 and NF-B by hypoxia may contribute to muscle adaptation in response to hypoxic conditions.

myotubes; calcium release; reactive oxygen species; transcription factors; ryanodine receptors; L-type calcium channel