Sublytic terminal complement attack induces c-fos transcriptional activation in myotubes

J Neuroimmunol. 2003 Sep;142(1-2):58-66. doi: 10.1016/s0165-5728(03)00261-3.

Abstract

Sublytic C5b-9 alters the molecular phenotype of myotubes by inhibiting muscle-specific gene expression. Here, we showed that C5b-9 induced c-fos mRNA and transcription. Using c-fos promoter-CAT constructs and electrophoretic mobility shift assay (EMSA), the minimal c-fos promoter activity was shown to increase within 30-min exposure to serum C5b-9, which also induced the binding of serum response factor (SRF), along with ternary complex factor (TCF) Elk1 and Sap1a to the serum response element. C5b-9 activated ERK1, which in turn activated Elk1 in myotubes. We propose that c-fos gene transcription associated with myotube dedifferentiation is induced by C5b-9 through ERK1-mediated assembly of serum response factor-ternary complex.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Animals
  • Cell Differentiation / genetics
  • Cell Differentiation / immunology
  • Cell Line
  • Complement Membrane Attack Complex / physiology*
  • DNA / metabolism
  • DNA-Binding Proteins / metabolism
  • Enzyme Activation / genetics
  • Enzyme Activation / immunology
  • Gene Expression Regulation / immunology*
  • Genes, fos / immunology*
  • Humans
  • Lymphoid Enhancer-Binding Factor 1
  • Mice
  • Mitogen-Activated Protein Kinase 3
  • Mitogen-Activated Protein Kinases / metabolism
  • Muscle, Skeletal / cytology
  • Muscle, Skeletal / enzymology
  • Muscle, Skeletal / immunology*
  • Muscle, Skeletal / metabolism*
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism
  • Phosphorylation
  • Protein Binding / genetics
  • Protein Binding / immunology
  • Proto-Oncogene Proteins / metabolism
  • Proto-Oncogene Proteins c-fos / genetics
  • Proto-Oncogene Proteins c-fos / metabolism
  • Response Elements / immunology
  • Serum Response Factor / metabolism
  • Signal Transduction / genetics
  • Signal Transduction / immunology
  • Transcription Factors / metabolism
  • Transcriptional Activation / immunology*
  • ets-Domain Protein Elk-1

Substances

  • Complement Membrane Attack Complex
  • DNA-Binding Proteins
  • ELK1 protein, human
  • Elk1 protein, mouse
  • Lymphoid Enhancer-Binding Factor 1
  • Nuclear Proteins
  • Proto-Oncogene Proteins
  • Proto-Oncogene Proteins c-fos
  • Serum Response Factor
  • Transcription Factors
  • ets-Domain Protein Elk-1
  • DNA
  • Mitogen-Activated Protein Kinase 3
  • Mitogen-Activated Protein Kinases