TY - JOUR

T1 - Procholecystokinin expression and processing in cardiac myocytes

AU - Goetze, Jens P

AU - Rehfeld, Jens F

N1 - Copyright © 2018 Elsevier Inc. All rights reserved.

PY - 2019

Y1 - 2019

N2 - The mammalian heart is by now an established endocrine organ whose myocytes in a regulated manner release atrial and ventricular natriuretic peptides (ANP and BNP). But like other hormone-producing cells in classic endocrine organs, the cardiac myocytes also express genes of additional peptide hormones. One such hormone gene is that of the well-known pleiotropic gut-brain peptide system, cholecystokinin (CCK), which is expressed at mRNA and protein levels in both atrial and ventricular cardiac myocytes. The posttranslational processing of proCCK in the myocytes, however, deviates substantially from that of other CCK-producing cells. Hence, the predominant cardiac proCCK product is devoid of the N-terminal 1-24 fragment, and besides O-sulfated at three C-terminal tyrosyl residues (Y76, Y90, and Y92). Moreover, carboxyamidated CCK peptides are present only in very low trace amounts (≤0.1%) in comparison with the truncated and triple-sulfated proCCK fragment. The present review first summarizes present knowledge about the wide-spread expression of the CCK system in mammals, and then discusses the possible function and biomarker role of the specific cardiac proCCK variant. The review concludes that the many unsettled questions about the specific cardiac expression cascade as well as the functional and diagnostic roles of cardiac CCK are worth pursuing.

AB - The mammalian heart is by now an established endocrine organ whose myocytes in a regulated manner release atrial and ventricular natriuretic peptides (ANP and BNP). But like other hormone-producing cells in classic endocrine organs, the cardiac myocytes also express genes of additional peptide hormones. One such hormone gene is that of the well-known pleiotropic gut-brain peptide system, cholecystokinin (CCK), which is expressed at mRNA and protein levels in both atrial and ventricular cardiac myocytes. The posttranslational processing of proCCK in the myocytes, however, deviates substantially from that of other CCK-producing cells. Hence, the predominant cardiac proCCK product is devoid of the N-terminal 1-24 fragment, and besides O-sulfated at three C-terminal tyrosyl residues (Y76, Y90, and Y92). Moreover, carboxyamidated CCK peptides are present only in very low trace amounts (≤0.1%) in comparison with the truncated and triple-sulfated proCCK fragment. The present review first summarizes present knowledge about the wide-spread expression of the CCK system in mammals, and then discusses the possible function and biomarker role of the specific cardiac proCCK variant. The review concludes that the many unsettled questions about the specific cardiac expression cascade as well as the functional and diagnostic roles of cardiac CCK are worth pursuing.

U2 - 10.1016/j.peptides.2018.06.001

DO - 10.1016/j.peptides.2018.06.001

M3 - Review

C2 - 29902521

VL - 111

SP - 71

EP - 76

JO - Peptides

JF - Peptides

SN - 0196-9781

ER -