Showing papers by "Karl L. Reichelt published in 1988"
TL;DR: A series of experiments are started to purify and characterize the putative inhibitor(s) of epidermal cell proliferation in vivo and in vitro, and to demonstrate the local control of cell renewal according to a negative feedback principle.
Abstract: The epidermal thickness is different in the various regions of the body, and from one species to another. But for a given region in a given species the normal thickness is remarkably constant throughout adult life. The corollary of this commonplace observation is that the cells that are lost from the surface are continually replaced by an equal number of new cells. Thus, the local control of cell renewal must be able to register quantitatively the need for new cells at any given time. A growth regulation of this type is best explained in terms of a negative feedback control. A stimulatory signal from already desquamated cells is physically impractical. Most available in vivo data support the concept that regulation of normal cell renewal basically works according to a negative feedback principle. Although such a regulation could involve a large number of interacting factors it presupposes the production of one or more mitosis inhibitors by cells that belong to the same tissues in which they act. In such a system, loss of inhibitor-producing cells is followed by a corresponding fall in inhibitor concentration and hence, a compensatory increase in cell production. Earlier experiments have shown that crude or partially purified skin extracts reversibly inhibit epidermal cell proliferation in vivo and in vitro.’ Experiments with such extracts indicated that proliferating epidermal cells were inhibited at several phases in the cell cycle,2 and that the effect was confined to keratinizing e~ithelia.~ Such experiments cannot, however, prove the existence of specific growth inhibitors, and we therefore started a series of experiments to purify and characterize the putative inhibitor(s).
13 citations
TL;DR: Extracts of mouse intestine contain a colonic epithelial mitosis inhibitor that has recently been purified and identified as a tripeptide (pGlu-His-GlyOH), which was found to have a bellshaped relationship with loss of inhibitory effect at high or low doses.
Abstract: 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 10−8 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.
11 citations
TL;DR: The possible tissue specificity of the colon mitosis inhibitor was examined and three structurally related bioactive peptides were tested and compared to the effect of CMI to investigate whether the amino acid sequence of the tripeptide is essential for the inhibitory effect.
Abstract: Previous work indicates that the colonic epithelial cell proliferation in mice is reversibly inhibited by the tripeptide pGlu-His-GlyOH found in aqueous extracts of the intestine. In the present study we examined the possible tissue specificity of the colon mitosis inhibitor. The mitotic rate in the small intestine, epidermis and forestomach in mice was registered after a single i.p. injection of the tripeptide. A significantly reduced rate of cell renewal was found at 18 h in the epidermis whereas no inhibition was observed in the forestomach or ileal epithelium. To investigate whether the amino acid sequence of the tripeptide is essential for the inhibitory effect, three structurally related bioactive peptides were tested and compared to the effect of CMI. CMI showed a bell-shaped dose-response relationship as previously shown, whereas the mitotic rate was not reduced in the colonie epithelium after treatment with either an epidermal mitosis inhibitory pentapeptide, or the dipeptide pGlu-GlyOH, or an analogue of luteinizing hormone-releasing hormone. The efficacy of the tripeptide was dependent on the basal rate of cell renewal in the colonie epithelium. When the tripeptide was given at the circadian nadir of cell proliferation a delayed reduction of the proliferative activity was observed at 6 h after treatment, whereas treatment when the rate of cell proliferation was at its circadian zenith gave an immediate mitotic inhibition.
9 citations