ERK1/2 and p38-MAPK signalling pathways, through MSK1, are involved in NF-κB transactivation during oxidative stress in skeletal myoblasts

Eirini Kefaloyianni, Catherine Gaitanaki, Isidoros Beis

Research output: Contribution to journalArticle

196 Scopus citations

Abstract

Skeletal muscle is highly adapted to respond to oxidative imbalances, since it is continuously subjected to an increased production of reactive oxygen species (ROS) during exercise. Oxidative stress, however, has been associated with skeletal muscle atrophy and damage in many diseases. In this study, we examined whether MAPK and NF-κB pathways participate in the response of skeletal myoblasts to oxidative stress, and whether there is a cross talk between these pathways. H2O2 induced a strong activation of ERKs, JNKs and p38-MAPK in a time- and dose-dependent profile. ERK and JNK activation by H2O2, but not that of p38-MAPK, was mediated by Src kinase and, at least in part, by EGFR. H2O2 also stimulated a mild translocation of NF-κB to the nucleus, as well as a moderate phosphorylation of its endogenous cytoplasmic inhibitor IκB (at Ser32/36), without any significant decrease in IκB total levels. Moreover, oxidative stress induced a strong phosphorylation of NF-κB p65 subunit at Ser536 and Ser276. Inhibition of MAPK pathways by selective inhibitors did not appear to affect H2O2-induced nuclear translocation of NF-κB or the phosphorylation of IκB. In contrast, phosphorylation of p65 at Ser276 was found to be mediated by MSK1, a substrate of both ERKs and p38-MAPK. In conclusion, it seems that, during oxidative stress, NF-κB translocation to the nucleus is most likely not related with the MAPK activation, while p65 phosphorylations are in part mediated by MAPKs pathways, probably modifying signal specificity.

Original languageEnglish
Pages (from-to)2238-2251
Number of pages14
JournalCellular Signalling
Volume18
Issue number12
DOIs
StatePublished - Dec 1 2006
Externally publishedYes

Keywords

  • MAPK
  • MSK1
  • Myoblasts
  • NF-κB
  • Oxidative stress
  • Signal transduction

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