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Opioid peptide gene expression primes cardiogenesis in embryonal pluripotent stem cells

Ventura, Carlo and Maioli, Margherita (2000) Opioid peptide gene expression primes cardiogenesis in embryonal pluripotent stem cells. Circulation Research, Vol. 87 (3), p. 189-194. eISSN 1524-4571. Article.

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Zinc finger– containing transcription factor GATA-4 and homeodomain Nkx-2.5 govern crucial developmental fates and have been found to promote cardiogenesis in embryonic cells exposed to the differentiating agent DMSO. Nevertheless, intracellular activators of these transcription factors are largely unknown. In this study, pluripotent P19 cells expressed the prodynorphin gene, an opioid gene encoding for the dynorphin family of opioid peptides. P19 cells were also able to synthesize and secrete dynorphin B, a biologically active end product of the prodynorphin gene. DMSO-primed GATA-4 and Nkx-2.5 gene expression was preceded by a marked increase in prodynorphin gene expression and dynorphin B synthesis and secretion. The DMSO effect occurred at the transcriptional level. In the absence of DMSO, dynorphin B triggered GATA-4 and Nkx-2.5 gene expression and led to the appearance of both α-myosin heavy chain and myosin light chain-2V transcripts, two markers of cardiac differentiation. Moreover, dynorphin B–exposed cells were positively stained in the presence of MF 20, a mouse monoclonal antibody raised against the α-myosin heavy chain. Opioid receptor antagonism and inhibition of opioid gene expression by a prodynorphin antisense phosphorothioate oligonucleotide blocked DMSO-induced cardiogenesis, suggesting an autocrine role of an opioid gene in developmental decisions.

Item Type:Article
ID Code:909
Uncontrolled Keywords:Opioid gene expression, myocardial development, transcription factors, stem cells
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:© 2000 American Heart Association
Deposited On:18 Aug 2009 10:03

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