© 2000 American Heart Association, Inc.
Molecular Medicine |
Opioid Peptide Gene Expression Primes Cardiogenesis in Embryonal Pluripotent Stem Cells
From the Department of Biomedical Sciences, Division of Biochemistry, Laboratory of Cardiovascular Research, University of Sassari, Sassari, Italy, and National Laboratory of the National Institute of Biostructures and Biosystems, Osilo, Italy.
Correspondence to Carlo Ventura, MD, PhD, Department of Biomedical Sciences, Division of Biochemistry, University of Sassari, Viale San Pietro 43/B, 07100 Sassari, Italy. E-mail chim_med{at}ssmain.uniss.it
Abstract—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 
-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 -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.
Key Words: opioid gene expression • myocardial development • transcription factors • stem cells
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