Purified Epidermal Pentapeptide Inhibits Proliferation and Enhances Terminal Differentiation in Cultured Mouse Epidermal Cells (original) (raw)
Related papers
Peptides' role in autism with emphasis on exorphins
2012
Problem: The nature of the peptides found increased in urine from autism needs verification of their structure, especially those that show opioid activity. Methods: The peptides were separated on reverse phase C-18 HPLC in Trifluoroacetic acidÁacetonitril gradients. Peaks eluting where synthetic opioids appear, and peaks that are common to most autistic children were analyzed by mass spectrometry and fragmentation pattern on a quadropole mass-spectrometer. Results: We could demonstrate exorphins in the urine from autistic children, and their length varied from one patient to the next. Conclusion: Exorphins are found in urine of autistic children and may account for their symptoms.
Autistic Syndromes and Diet: a follow‐up study
Scandinavian Journal of Educational Research, 1995
Problem: Some researchers have not found the opioids in urine of autistic children. We have therefore looked at this problem again. Method: Mass spectrometry and fragmentation mass spectrometry (MS/MS) have been carried out on peaks from the HPLC that show co-chromatography with synthetic standards and peaks that are shared by different autistic children. Results: In quickly frozen urine we find the presence of exorphins, and can also demonstrate a rather fast break down at room temperature of these peptides in urine. Conclusion: Exorphins are present in urine in autistic children, but must be protected against break down and aggregation by fast freezing or acetic acid and adjusting declustering potential and collision potential during mass-spectroscopy. Specific antibody increases and the effect of removing precursor proteins from the diet reinforce this view.
Experimental Cell Research, 1998
Cell growth and differentiation in melanocyte cell populations are regulated by a wide range of bioactive substances. Recently, the tripeptide pyroGlu-Phe-GlyNH2 which inhibits melanocyte growth in vitro was identified in both murine nontransformed melanocytes and malignant melanoma cells. The present study was undertaken to investigate the cell cycle specificity as well as the growth inhibitory profile of the tripeptide after a single or repeated administration to melanocyte cultures. Dose-related effects of the peptide were studied using three different bioassay systems: estimation of cell number, DNA synthesis, and cell flux into mitosis. Growth of melanocyte cultures as well as melanocyte mitotic activity were found to be reduced significantly by the tripeptide at two separate dose levels (10(-11) and 10(-14)-10(-15) M). Growth inhibition of melanocyte population did not last long: less than 36 h after the first and less than 24 h after the second peptide addition to the cultures. The level of DNA synthesis in melanocytes remained unchanged after a single peptide administration. The findings indicate that the tripeptide pyroGlu-Phe-GlyNH2 causes transitory delay of cell growth in cultured melanocyte population resulting from a reversible inhibition of melanocyte transition from the G2-phase of the cell cycle into mitosis.
Isolation of a growth and mitosis inhibitory peptide from mouse liver
Virchows Archiv B Cell Pathology Including Molecular Pathology, 1990
The isolation of a liver peptide that inhibits the growth, mitosis rate and thymidine incorporation in regenerating liver is described. The peptide has the structure Pyroglu-gln-gly-ser-asn, and the deamidated forms are also active. The peptide probably belongs to a class of growth inhibitors with a high degree of tissue specificity. Two such peptides have previously been isolated from the epidermis ) and from colonic tissue .
Virchows Archiv. B, Cell pathology including molecular pathology, 1991
A transformed mouse epidermal cell line ("308 cells") and nontransformed rat tongue squamous epithelial cells ("RT10 cells") were treated 3 times weekly for a period of two weeks with relatively large doses (150 micrograms/ml) of a synthetic inhibitory epidermal pentapeptide; pyroGlu-Glu-Asp-Ser-GlyOH. The peptide was recently isolated from mouse skin extracts and inhibits normal epidermal cells in vivo and in vitro at a restricted and low dose level. Repeated treatments with the large dose was followed by a 30-40% reduction in the number of 308 cells per well, starting as early as day 1. The number of RT10 cells was reduced about 20% only at termination of the experiment on day 14. In contrast to this, the number of unattached cornified envelopes on day 10 in the RT10 cells was increased by 85%, while the number of cornified, unattached 308 cells was similar to that in the controls. The effects of the pentapeptide thus seem to affect differentiation stronger tha...
PLoS Pathogens, 2011
The herpesviruses, like most other DNA viruses, replicate in the host cell nucleus. Subnuclear domains known as promyelocytic leukemia protein nuclear bodies (PML-NBs), or ND10 bodies, have been implicated in restricting early herpesviral gene expression. These viruses have evolved countermeasures to disperse PML-NBs, as shown in cells infected in vitro, but information about the fate of PML-NBs and their functions in herpesvirus infected cells in vivo is limited. Varicellazoster virus (VZV) is an alphaherpesvirus with tropism for skin, lymphocytes and sensory ganglia, where it establishes latency. Here, we identify large PML-NBs that sequester newly assembled nucleocapsids (NC) in neurons and satellite cells of human dorsal root ganglia (DRG) and skin cells infected with VZV in vivo. Quantitative immuno-electron microscopy revealed that these distinctive nuclear bodies consisted of PML fibers forming spherical cages that enclosed mature and immature VZV NCs. Of six PML isoforms, only PML IV promoted the sequestration of NCs. PML IV significantly inhibited viral infection and interacted with the ORF23 capsid surface protein, which was identified as a target for PML-mediated NC sequestration. The unique PML IV C-terminal domain was required for both capsid entrapment and antiviral activity. Similar large PML-NBs, termed clastosomes, sequester aberrant polyglutamine (polyQ) proteins, such as Huntingtin (Htt), in several neurodegenerative disorders. We found that PML IV cages co-sequester HttQ72 and ORF23 protein in VZV infected cells. Our data show that PML cages contribute to the intrinsic antiviral defense by sensing and entrapping VZV nucleocapsids, thereby preventing their nuclear egress and inhibiting formation of infectious virus particles. The efficient sequestration of virion capsids in PML cages appears to be the outcome of a basic cytoprotective function of this distinctive category of PML-NBs in sensing and safely containing nuclear aggregates of aberrant proteins.
Virchows Archiv B Cell Pathology Including Molecular Pathology, 1988
Extracts of mouse intestine contain a colonic epithelial mitosis inhibitor that has recently been purified and identified as a tripeptide (pGlu-His-GlyOH). In order to elucidate further the biological characteristics of this peptide, the effect of the tripeptide on cell proliferation in a human colon carcinoma cell line (HT 29) was examined. The incorporation of tritiated thymidine was significantly reduced at 20-30 h after addition of the tripeptide. The dose-response relationship was bellshaped with loss of inhibitory effect at high or low doses. The number of cells were significantly reduced at a peptide concentration of l0 -8 M at 24 h, but not at 48 or 72 h after addition of the peptide. The inhibition was reversible, and was only observed when the cells were grown in a serum-restricted medium (1%). The inhibitory effect was abolished by increasing the serum content to 10% or adding insulin to the medium.
Virchows Archiv. B, Cell pathology including molecular pathology, 1990
Earlier work has shown that epidermal cells contain a peptide, pyroGlu-Glu-Asp-Ser-GlyOH, that induces a moderate but long-lasting inhibition of epidermal cell proliferation when given at low (picomol) doses ip in vivo and in vitro. In the present study, the epidermal pentapeptide was applied topically to the back skin of hairless mice at different concentrations and in a water-miscible cream. A single topical application of either high (0.25% wt/wt) or low (0.004% or 0.02% wt/wt) doses of the pentapeptide was followed by oscillations in epidermal DNA synthesis and G2-M cell flux (mitotic rate). In general, epidermal cell proliferation was inhibited during the first 10-day period after treatment with the two lower doses, while the highest concentration of pentapeptide (0.25%) stimulated epidermal cell proliferation. In spite of the effects on epidermal cell proliferation the size of the epidermal cell population in the treated area (number of nucleated cells and epidermal thickness)...
Cooperative Hedgehog-EGFR signaling
Frontiers in Bioscience, 2012
It has been known for many years that cooperative interactions between oncogenes (e.g. RAS, MYC, BCL2) can fuel cancer growth (1-5), but the restricted druggability of many of those interacting cancer genes has hampered translation of combined targeting to medical cancer therapy. The identification and characterization of cooperative cancer signaling pathways amenable to medical therapy is therefore a crucial step towards the establishment of efficient targeted combination treatments urgently needed to improve cancer therapy. Here we review recent findings of our group and colleagues on the molecular mechanisms of cooperative Hedgehog/GLI and Epidermal Growth Factor Receptor (EGFR) signaling, two clinically relevant oncogenic pathways involved in the development of many human malignancies. We also discuss the possible implications of these findings for the design of a therapeutic regimen relying on combined targeting of key effectors of both pathways.