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Protein kinase C signaling transduces endorphin-primed cardiogenesis in GTR1 embryonic stem cells

Ventura, Carlo and Zinellu, Elisabetta and Maninchedda, Emiliana and Fadda, Marina and Maioli, Margherita (2003) Protein kinase C signaling transduces endorphin-primed cardiogenesis in GTR1 embryonic stem cells. Circulation Research, Vol. 92 (6), p. 617-622. eISSN 1524-4571. Article.

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DOI: 10.1161/01.RES.0000065168.31147.5B


The prodynorphin gene and its product, dynorphin B, have been found to promote cardiogenesis in embryonic cells by inducing the expression of GATA-4 and Nkx-2.5, two transcription factor–encoding genes essential for cardiogenesis. The molecular mechanism(s) underlying endorphin-induced cardiogenesis remain unknown. In the present study, we found that GTR1 embryonic stem (ES) cells expressed cell surface opioid receptors, as well as protein kinase C (PKC)-α, -ß1, -ß2, -δ, -ε, and -ζ. Cardiac differentiation was associated with a marked increase in the Bmax value for a selective opioid receptor ligand and complex subcellular redistribution of selected PKC isozymes. PKC-α, -ß1, -ß2, -δ, and -ε all increased in the nucleus of ES-derived cardiac myocytes, compared with nuclei from undifferentiated cells. In both groups of cells, PKC-δ and -ε were mainly expressed at the nuclear level. The nuclear increase of PKC-α, -ß1, and -ß2 was due to a translocation from the cytosolic compartment. In contrast, the increase of both PKC-δ and PKC-ε in the nucleus of ES-derived cardiomyocytes occurred independently of enzyme translocation, suggesting changes in isozyme turnover and/or gene expression during cardiogenesis. No change in PKC-ζ expression was observed during cardiac differentiation. Opioid receptor antagonists prevented the nuclear increase of PKC-α, PKC-ß1, and PKC-ß2 and reduced cardiomyocyte yield but failed to affect the nuclear increase in PKC-δ and -ε. PKC inhibitors prevented the expression of cardiogenic genes and dynorphin B in ES cells and abolished their development into beating cardiomyocytes.

Item Type:Article
ID Code:754
Uncontrolled Keywords:Protein kinase C, cardiac differentiation, embryonic stem cells, gene expression, endorphins
Subjects:Area 05 - Scienze biologiche > BIO/10 Biochimica
Divisions:001 Università di Sassari > 01 Dipartimenti > Scienze biomediche
002 Altri enti e centri di ricerca del Nord Sardegna > National laboratory of the national institute of biostructures and biosystems, Osilo
Publisher:Lippincott Williams & Wilkins
Copyright Holders:© 2003 American Heart Association
Deposited On:18 Aug 2009 10:03

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