Nitric Oxide Induces Gene Expression of Jumonji and Retinoblastoma 2 Protein while Reducing Expression of Atrial Natriuretic Peptide Precursor Type B in Cardiomyocytes (jumonji / nitric oxide / cardiomyocyte / heart / atrial natriuretic peptides / retinoblastoma)

Jumonji (JMJ, Jarid2), a prototypical member of the jumonji domain-containing protein family, plays a major role in embryonic cardiac de- velopment, but its role in the developed heart is un- clear. Cardiomyocytes from neonatal mouse heart were treated in culture with NO donor SIN-1, 500 μM, for 2, 4, and 20 h. SIN-1 treatment was associ- ated with a significant and 6.9 ± 2.5 fold increase in jmj gene expression over all time points. The expres- sion of jmj increased markedly and significantly 4.2 ± 1.1 fold, 16.6 ± 4.1 fold, and 2.7 ± 0.3 fold, respec- tively, at time points 2 h, 4 h, and 20 h after treat- ment. The ability of the increase in gene expression to translate into an increase in cellular protein ex- pression 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 sig- nificant 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 pep- tide 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 me- diates some of the cellular effects of NO, that NO may be able to increase JMJ in diseases associated with reduced JMJ expression.