F1-ATP Synthaseβ-Subunit and CytochromecTranscriptional Regulation in Right Ventricular Hemodynamic Overload and Hypertrophically Stimulated Cardiocytes

Cardiac hypertrophic growth secondary to hemodynamic pressure overload causes changes in energy requirements that may involve the transcriptional upregulation of oxidative phosphorylation genes. Therefore, two representative nuclear-encoded genes, the mitochondrial F1-ATP synthaseβ-subunit (β-subunit) and cytochromec(cytc), were examined in a feline chronic pulmonary artery banded right ventricular pressure-overload model. In the hypertrophying right ventricle,β-subunit and cytcmRNA levels increased after two and seven days, during the peak growth response. To examine cardiac transcriptional regulation, neonatal rat cardiac myocytes (cardiocytes) were transiently transfected withβ-subunit promoter constructs ranging from −1519 nucleotides (nt) upstream of transcription initiation as well as cytcpromoter constructs ranging from −726 nt. A full-length p1519β-subunit/Luc construct wasα-adrenergically inducible by 275% (±30%) with this activation being mapped to an enhancer region between −1519 to −1480 nt. Smaller constructs containing more proximal promoter elements were not inducible. Additionally, the full-length and enhancer deletedβ-subunit constructs were also inducible in electrically stimulated cardiocytes, suggesting a different mechanism of activation. Cytcconstructs containing known constitutive elements from −191 to −167 nt and −139 to −84 nt were responsible for the majority of the reporter activity of the full-length promoter but were not inducible in the presence of phenylephrine. Hence, we show that promoter regions containing elements common in other metabolism-related gene families are active in neonatal rat cardiocytes. Once more, we have identified aβ-subunit genomic region responsive toα-adrenergic and electrical stimulation.