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Cardiomyocyte expression and cell-specific processing of procholecystokinin

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@article{727a0d56c1c642f7ac779b9e5da51d05,
title = "Cardiomyocyte expression and cell-specific processing of procholecystokinin",
abstract = "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.",
keywords = "Aged, Aged, 80 and over, Amino Acid Sequence, Animals, Cardiotonic Agents, Cell Line, Cholecystokinin, Female, Gene Expression, Heart Failure, Humans, Isoproterenol, Male, Middle Aged, Molecular Sequence Data, Myocytes, Cardiac, Prognosis, Protein Precursors, Rats, Swine",
author = "Goetze, {Jens P} and Johnsen, {Anders H} and Caroline Kistorp and Finn Gustafsson and Johnbeck, {Camilla B} and Rehfeld, {Jens F}",
note = "{\circledC} 2015 by The American Society for Biochemistry and Molecular Biology, Inc.",
year = "2015",
month = "3",
day = "13",
doi = "10.1074/jbc.M114.622670",
language = "English",
volume = "290",
pages = "6837--43",
journal = "Journal of Biological Chemistry",
issn = "0021-9258",
publisher = "American Society for Biochemistry and Molecular Biology, Inc",
number = "11",

}

RIS

TY - JOUR

T1 - Cardiomyocyte expression and cell-specific processing of procholecystokinin

AU - Goetze, 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

VL - 290

SP - 6837

EP - 6843

JO - Journal of Biological Chemistry

JF - Journal of Biological Chemistry

SN - 0021-9258

IS - 11

ER -

ID: 45860385