Cardiomyocyte expression and cell-specific processing of procholecystokinin [Gene Regulation]

January 27th, 2015 by Goetze, J. P., Johnsen, A. H., Kistorp, C., Gustafsson, F., Johnbeck, C. B., Rehfeld, J. F.

Heart muscle cells produce peptide hormones such as natriuretic peptides. Developing hearts also express the gene for the classic gut hormone cholecystokinin (CCK) in amounts similar to those of the gut and the brain. However, cardiac expression of other peptides than natriuretic peptides has only been suggested using transcriptional measures or methods with the post-translational phase of gene expression unaddressed. In this study, we examined the cardiac expression of the CCK gene in adult mammals and its expression at protein level. By quantitative PCR, a library of sequence-specific proCCK assays, peptide purification, and mass spectrometry, we demonstrate that the mammalian heart expresses proCCK in amounts comparable to natriuretic prohormones and processes it to a unique triple-sulfated and N-terminally truncated product distinct from intestinal and cerebral CCK peptides. Isoprenaline rapidly stimulates cardiac CCK gene expression in vitro and in vivo, which suggests that the cardiac-specific truncated proCCK may have pathophysiological relevance as a new marker of heart failure. The suggestion is confirmed by measurement in plasma from heart failure patients.