Opioid gene expression in the developing and adult rat heart

Abstract

Opioid peptides are known to play a role in the function and growth of the mammalian heart. Although some information about gene expression of opioids in the heart is available, there is no data on the cellular location of opioid gene expression during development or in the adult. Using in situ hybridization and rat heart ranging from embryonic day 14 (E14) to adulthood, we have evaluated the distribution of gene expression for proenkephalin, proopiomelanocortin, and prodynorphin. With respect to preproenkephalin mRNA (PPE mRNA), message in the ventricle was abundant from E14 (the first time point examined) until shortly after birth, with a marked reduction noted on postnatal days 5, 10, and 21. Adults displayed considerable message, though less than in preparations of embryonic and neonatal heart. PPE mRNA was detected in epicardial, myocardial, and endocardial cells, as well as the walls of blood vessels, capillaries, and fibroblasts. Preproopiomelanocortin (POMC) mRNA was only found in adults, and was localized to the myocardium. Message for preprodynorphin could not be observed in the ventricles of developing or adult rats. These results are the first to define the temporal and spatial ontogeny of opioid gene expression with regard to the emergence of cardiac architecture. The data suggest that gene expression for proenkephalin is especially prevalent in embryonic and neonatal rats and may be related to the modulatory activity of the opioid growth factor, [Met5]‐enkephalin, on cell proliferation and differentiation. The role of PPE and POMC mRNA in adult rat heart requires elucidation. Dev. Dyn. 1998;211:153–163. © 1998 Wiley‐Liss, Inc.

Molecular Fingerprinting and Autocrine Growth Regulation of Endothelial Cells in a Murine Model of Hepatocellular Carcinoma

“…We identified 156 genes/ESTs being Other genes that have previously been implicated in neovascularization and are up-regulated in LTECs include myelocytomas oncogene (myc) and B-cell translocation gene 1 (btg1), both regulators of cell growth and angiogenesis (39,40). Preproenkephalin (Penk1) encodes opioid growth factor, which is important for embryonic vessel development (41), as is spleen tyrosine kinase (Syk; ref. 42).…”

The OGF–OGFr Axis Utilizes the p16INK4aand p21WAF1/CIP1Pathways to Restrict Normal Cell Proliferation

“…OGF is a constitutively expressed native opioid that is autocrine produced and secreted to inhibit the growth of both normal cells McLaughlin, 1987, 1991;Hauser et al, 1990;Stiene-Martin and Hauser, 1990;Hauser and Stiene-Martin, 1991;Isayama et al, 1991;Villiger and Lotz, 1992;Zagon et al, 1994Zagon et al, , 1995aZagon et al, ,b, 1996aZagon et al, , 1997aZagon et al, ,b, 1998Zagon et al, , 1999bZagon et al, , 2000bMcLaughlin, 1996;Vertes et al, 1996;McLaughlin and Wu, 1998;Blebea et al, 2000;Wilson et al, 2000;Kornyei et al, 2003;Robertson and Andrew, 2003;Malendowicz et al, 2005) and cancer cells (Zagon et al, 1996c;Cheng et al, 2007Cheng et al, , 2008. The action of OGF is tonic, stereospecific, reversible, noncytotoxic, and nonapoptotic inducing, is not associated with differentiative, migratory, invasive, or adhesive processes, is independent of serum, anchorage-independent and occurs at physiologically relevant concentrations (Zagon et al, , 2007a, 2004.…”

“…The action of the OGF-OGFr axis in normal and cancer cells is targeted to DNA synthesis McLaughlin, 1987, 1991;Isayama et al, 1991;Zagon et al, 1994Zagon et al, , 1995bZagon et al, , 2000aMcLaughlin, 1996;McLaughlin and Wu, 1998;McLaughlin et al, 1999;Wilson et al, 2000;Blebea et al, 2002). In squamous cell carcinoma of the head and neck, OGF activity has been shown to be dependent on one CKI, p16…”

“…Because OGF depresses DNA synthesis and subsequent cell/tissue growth in a wide variety of normal and developing cells in humans and animals, including ectodermal, mesodermal, and endodermal derivatives Hauser and Stiene-Martin, 1991;Isayama et al, 1991;Zagon and McLaughlin, 1991;Zagon et al, 1994Zagon et al, , 1995bZagon et al, , 1996aZagon et al, ,b, 1997Zagon et al, , 1999bMcLaughlin, 1996;Vertes et al, 1996;McLaughlin and Wu, 1998;Blebea et al, 2000Blebea et al, , 2002Wilson et al, 2000;Kornyei et al, 2003), the question arises as to the mechanism of peptide action on the cell cycle in these cells. The present investigation examined the specific target(s) in the cell cycle for the OGF-OGFr axis in cells derived from four normal human tissues: umbilical vein endothelial This article was published online ahead of print in MBC in Press (http://www.molbiolcell.org/cgi/doi/10.1091/mbc.E08 -07-0681) on October 15, 2008. cells (HUVECs), epidermal keratinocytes (NHEKs), dermal fibroblasts (NHDFs), and mesenchymal stem cells (hMSCs).…”

Far‐upstream elements are dispensable for tissue‐specific proenkephalin expression using a Cre‐mediated knock‐in strategy

“…The cellular levels of enkephalin peptides are the result of complex regulatory processes including transcriptional, post‐transcriptional and post‐translational controls. A striking example is the heart, which expresses moderate levels of ENK mRNA with little detectable production of enkephalin peptides (Rao and Howells 1992; McLaughlin and Allar 1998; McLaughlin and Wu 1998).…”