Activation of the cytochrome c gene by electrical stimulation in neonatal rat cardiac myocytes. Role of NRF-1 and c-Jun

J Biol Chem. 1998 May 15;273(20):12593-8. doi: 10.1074/jbc.273.20.12593.


Activation of cytochrome c (cyt c) transcription in electrically stimulated neonatal rat cardiac myocytes is preceded by transient expression of the activating protein-1 family of transcription factors, c-Fos, c-Jun, and JunB, as well as nuclear respiratory factor-1 (NRF-1). Mutations in either the NRF-1 or in the two cyclic AMP response elements on the cyt c promoter significantly reduce cyt c promoter activation produced either by electrical stimulation (Xia, Y., Buja, L. M., Scarpulla, R. C., and McMillin, J. B. (1997) Proc. Natl. Acad. Sci. U. S. A. 94, 11399-11404) or by transfection of c-jun into nonpaced cardiac myocytes. Electrical stimulation of cardiac myocytes activates the c-Jun N-terminal kinase (McDonough, P. M., Hanford, D. S., Sprenkle, A. B., Mellon, N. R., and Glembotski, C. C. (1997) J. Biol. Chem. 272, 24046-24053) so that the fold-activation of the cyt c promoter is increased by pacing when either c-jun or c-fos/c-jun were cotransfected. Physical association of NRF-1 protein with the NRF-1 enhancer element and of c-Jun with the cyclic AMP response element binding sites on the cyt c promoter was demonstrated by gel shift competition assays and by antibody super shifts. This is the first demonstration that induction of NRF-1 and c-Jun by pacing of cardiac myocytes directly mediates cyt c gene expression and mitochondrial proliferation in response to hypertrophic stimuli in the heart.

Publication types

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

MeSH terms

  • Animals
  • Animals, Newborn
  • Cells, Cultured
  • Cytochrome c Group / genetics*
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism*
  • Electric Stimulation
  • Myocardium / cytology
  • Myocardium / enzymology*
  • NF-E2-Related Factor 1
  • Nuclear Respiratory Factor 1
  • Nuclear Respiratory Factors
  • Promoter Regions, Genetic
  • Protein Binding
  • Proto-Oncogene Proteins c-jun / genetics
  • Proto-Oncogene Proteins c-jun / metabolism*
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Rats
  • Trans-Activators / genetics
  • Trans-Activators / metabolism*
  • Transcription Factor AP-1 / metabolism
  • Transcriptional Activation


  • Cytochrome c Group
  • DNA-Binding Proteins
  • NF-E2-Related Factor 1
  • Nfe2l1 protein, rat
  • Nuclear Respiratory Factor 1
  • Nuclear Respiratory Factors
  • Proto-Oncogene Proteins c-jun
  • RNA, Messenger
  • Trans-Activators
  • Transcription Factor AP-1