Nitric oxide induces gene expression of Jumonji and retinoblastoma 2 protein while reducing expression of atrial natriuretic peptide precursor type B in cardiomyocytes.
Jumonji (JMJ, Jarid2), a prototypical member of the jumonji domain-containing protein family, plays a major role in embryonic cardiac development, but its role in the developed heart is unclear. Cardiomyocytes from neonatal mouse heart were treated in culture with NO donor SIN-1, 500 microM, for 2, 4, and 20 h. SIN-1 treatment was associated with a significant and 6.9 +/- 2.5 fold increase in jmj gene expression over all time points. The expression of jmj increased markedly and significantly 4.2 +/- 1.1 fold, 16.6 +/- 4.1 fold, and 2.7 +/- 0.3 fold, respectively, at time points 2 h, 4 h, and 20 h after treatment. The ability of the increase in gene expression to translate into an increase in cellular protein expression was ascertained by Western blotting, which showed an increase in the JMJ protein in whole-cell lysates. Because of the relationship of JMJ to Rb and ANP in the heart, gene expression of these proteins was also examined. SIN-1 produced a small but significant increase in Rb2, but not Rb1 or Rb-binding proteins 4, 6, or 7. In contrast, SIN-1 produced a marked and significant reduction in natriuretic peptide precursor type B but not type C to 0.24 +/- 0.09 fold of the control. These data suggest that JMJ may be a critical, previously unrecognized factor that mediates some of the cellular effects of NO, that NO may be able to increase JMJ in diseases associated with reduced JMJ expression.
Klassen
S S
SS
Department of Medicine, University of British Columbia, Vancouver, BC, Canada.
Rabkin
S W
SW
D000818:Animals; D002478:Cells, Cultured; D005786:Gene Expression Regulation; D006321:Heart; D051379:Mice; D008981:Molsidomine / Q000031:analogs & derivatives / Q000494:pharmacology; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism*; D020097:Natriuretic Peptide, Brain / Q000235:genetics* / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000235:genetics* / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism*; D020030:Nitric Oxide Donors / Q000494:pharmacology; D020411:Oligonucleotide Array Sequence Analysis; D063151:Polycomb Repressive Complex 2; D050717:Retinoblastoma-Like Protein p130 / Q000235:genetics
C093650:Jarid2 protein, mouse; D009419:Nerve Tissue Proteins; D020030:Nitric Oxide Donors; C493837:RBL2 protein, human; D050717:Retinoblastoma-Like Protein p130; D020097:Natriuretic Peptide, Brain; D009569:Nitric Oxide; C002385:linsidomine; D008981:Molsidomine; D063151:Polycomb Repressive Complex 2