Activation of the cytochrome c gene by electrical stimulation in neonatal rat cardiac myocytes. Role of NRF-1 and c-Jun.
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.
Xia
Y
Y
Department of Pathology and Laboratory Medicine, University of Texas Medical School, Houston, Texas 77030, USA.
Buja
L M
LM
McMillin
J B
JB
D000818:Animals; D000831:Animals, Newborn; D002478:Cells, Cultured; D003574:Cytochrome c Group / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D004558:Electric Stimulation; D009206:Myocardium / Q000166:cytology / Q000201:enzymology*; D051265:NF-E2-Related Factor 1; D051266:Nuclear Respiratory Factor 1; D051264:Nuclear Respiratory Factors; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D016755:Proto-Oncogene Proteins c-jun / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*; D018808:Transcription Factor AP-1 / Q000378:metabolism; D015533:Transcriptional Activation
D003574:Cytochrome c Group; D004268:DNA-Binding Proteins; D051265:NF-E2-Related Factor 1; C495632:Nfe2l1 protein, rat; D051266:Nuclear Respiratory Factor 1; D051264:Nuclear Respiratory Factors; D016755:Proto-Oncogene Proteins c-jun; D012333:RNA, Messenger; D015534:Trans-Activators; D018808:Transcription Factor AP-1