Cardiomyocyte expression and cell-specific processing of procholecystokinin
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Cardiomyocyte expression and cell-specific processing of procholecystokinin. / Gøtze, Jens P.; Johnsen, Anders H.; Kistorp, Caroline; Gustafsson, Finn; Johnbeck, Camilla B; Rehfeld, Jens F.
In: The Journal of Biological Chemistry, Vol. 290, No. 11, 13.03.2015, p. 6837-43.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Cardiomyocyte expression and cell-specific processing of procholecystokinin
AU - Gøtze, Jens P.
AU - Johnsen, Anders H.
AU - Kistorp, Caroline
AU - Gustafsson, Finn
AU - Johnbeck, Camilla B
AU - Rehfeld, Jens F
N1 - © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.
PY - 2015/3/13
Y1 - 2015/3/13
N2 - Heart muscle cells produce peptide hormones such as natriuretic peptides. Developing hearts also express the gene for the classic intestinal hormone cholecystokinin (CCK) in amounts similar to those in the intestine and brain. However, cardiac expression of peptides other 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 the protein level. Using quantitative PCR, a library of sequence-specific pro-CCK assays, peptide purification, and mass spectrometry, we demonstrate that the mammalian heart expresses pro-CCK 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 stimulated cardiac CCK gene expression in vitro and in vivo, which suggests that the cardiac-specific truncated pro-CCK may have pathophysiological relevance as a new marker of heart failure. The suggestion is confirmed by measurement of plasma from heart failure patients.
AB - Heart muscle cells produce peptide hormones such as natriuretic peptides. Developing hearts also express the gene for the classic intestinal hormone cholecystokinin (CCK) in amounts similar to those in the intestine and brain. However, cardiac expression of peptides other 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 the protein level. Using quantitative PCR, a library of sequence-specific pro-CCK assays, peptide purification, and mass spectrometry, we demonstrate that the mammalian heart expresses pro-CCK 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 stimulated cardiac CCK gene expression in vitro and in vivo, which suggests that the cardiac-specific truncated pro-CCK may have pathophysiological relevance as a new marker of heart failure. The suggestion is confirmed by measurement of plasma from heart failure patients.
KW - Aged
KW - Aged, 80 and over
KW - Amino Acid Sequence
KW - Animals
KW - Cardiotonic Agents
KW - Cell Line
KW - Cholecystokinin
KW - Female
KW - Gene Expression
KW - Heart Failure
KW - Humans
KW - Isoproterenol
KW - Male
KW - Middle Aged
KW - Molecular Sequence Data
KW - Myocytes, Cardiac
KW - Prognosis
KW - Protein Precursors
KW - Rats
KW - Swine
U2 - 10.1074/jbc.M114.622670
DO - 10.1074/jbc.M114.622670
M3 - Journal article
C2 - 25627687
VL - 290
SP - 6837
EP - 6843
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
SN - 0021-9258
IS - 11
ER -
ID: 162376396