Abstract
A single intraperitoneal (i.p.) injection of picomolar doses of the epidermal pentapeptide (EPP), pGlu-Glu-Asp-Ser-GlyOH, is followed by a reversible inhibition of mouse epidermal cell proliferation. An equimolar mixture of zinc and EPP injected i.p. into hairless mice reversed the inhibitory activity, resulting in an immediate stimulation of epidermal G2-M cell flux. The stimulatory effect was strongest at the lowest dose (5 pmol). This effect was probably caused by a dizinc-dipentapeptide dimer, as shown by gel filtration and atomic emission spectrometry. When zinc was added in excess (EPP∶Zn 1∶9) no such dimer could be identified, and the mixture had no stimulatory effect. The results are discussed in terms of epidermal cell kinetics, and in relation to the use of zinc in dermatology.
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References
Bullough WS, Laurence EB (1960) The control of epidermal mitotic activity in the mouse. Proc R Soc Lond B Biol Sci 151: 517–536
Changelian PS, Feng P, King TC, Milbrandt J (1989) Structure of NGFI-A gene and detection of upstream sequences responsible for its transcriptional induction of nerve growth factor. Proc Natl Acad Sci USA 86: 377–381
Christy B, Nathans D (1989) DNA binding site of the growth factor-inducible protein Zi-f268. Proc Natl Acad Sci USA 86: 8737–8741
Clausen OPF, Thorud E, Bjerknes R, Elgjo K (1979) Circadian rhythms in mouse epidermal basal cell proliferation. Variations in compartment size, flux and phase duration. Cell Tissue Kinet 12: 319–337
Clausen OPF, Thorud E, Aarnaes E (1981) Evidence of rapid and slow progression of cells through G2 phase in mouse epidermis: a comparison between phase durations measured by different methods. Cell Tissue Kinet 14: 227–240
Day ML, Fahrner TJ, Aykent S, Milbrandt J (1990) The zinc finger protein NGFI-A exists in both nuclear and cytoplasmic forms in nerve growth factor-stimulated PC12 cells. J Biol Chem 265: 15253–15260
Dreno B, Trossaert M, Boiteau HL, Litoux P (1992) Évolution du zinc cutané au cours du vieillissement cutané. Ann Dermatol Venereol 119: 263–266
Elgjo K, Reichelt KL (1984) Purification and characterization of a mitosis inhibiting epidermal peptide. Cell Biol Int Rep 8: 379–382
Elgjo K, Reichelt KL, Edminson P, Moen E (1986) Endogenous peptides in epidermal growth control. In: Baserga R, Foa P, Metcalf D, Polli EE (eds) Biological regulation and cell proliferation. Raven Press, New York, pp 259–265
Elgjo K, Reichelt KL (1988) Structure and function of growth inhibitory epidermal pentapeptide. Ann NY Acad Sci 548: 197–203
Hennings H, Michael D, Cheng C, Steinert P, Holbrook K, Yuspa SH (1980) Calcium regulation of growth and differentiation of mouse epidermal cells in culture. Cell 19: 245–254
Iversen OH (1961) The regulation of cell numbers in epidermis. Acta Pathol Microbiol Scand Suppl 148: 91–96
Iversen OH, Evensen A (1962) Experimental skin carcinogenesis in mice. Acta Pathol Microbiol Scand Suppl 156: 1–184
Laerum OD, Sletvold O, Bjerknes R, Eriksen JA, Johansen JH, Schanche JS, Tveteraas T, Paukovits WR (1988) The dimer of hemoregulatory peptide (HP5b) stimulates mouse and human myelopoiesis in vitro. Exp Hematol 16: 274–280
Martin R-P, Mosoni L (1971) Ternary coordination complexes between glycine, copper(II), and glycine peptides in aqueous solution. J Biol Chem 10: 5944–5951
Michaelsson G, Ljunghall K (1990) Patients with dermatitis herpetiformis, acne, psoriasis and Darier's disease have low epidermal zinc concentrations. Acta Derm Venereol (Stockh) 70: 304–308
Nome O (1975) Tissue specificity of the epidermal chalones. Virchows Arch [B] Cell Pathol 19: 1–25
Östergren R (1970) The metal complexes of peptides and related compounds. Eur J Biochem 13: 493–503
Paukovits WR, Laerum OD (1982) Isolation and synthesis of a hemoregulatory peptide. Z Naturforsch [C] 37: 1297–1300
Paulsen JE, Reichelt KL, Petersen A (1987) Purification and characterization of a growth inhibitory hepatic peptide. Virchows Arch [B] Cell Pathol 54: 152–154
Reichelt KL, Kvamme E (1973) Histamine-dependent formation of N-acetyl-aspartyl peptides in mouse brain. J Neurochem 21: 849–859
Reichelt KL, Elgjo K, Edminson PD (1987) Isolation and structure of an epidermal mitosis inhibiting pentapeptide. Biochem Biophys Res Commun 146: 1493–1501
Skraastad O, Fossli T, Edminson P, Reichelt KL (1988) Purification and characterization of a mitosis inhibitory tripeptide from mouse intestinal extracts. Epithelia 1: 107–119
Watt FM, Hudson DL, Lamb AG, Bolsover SR, Silver RA, Aitchison MJ, Whitaker M (1991) Mitogens induce calcium transients in both dividing and terminally differentiating keratinocytes. J Cell Sci 99: 397–405
Young M, Blanchard MH, Sessions F, Boyle MDP (1988) Subunit structure of high molecular weight mouse nerve growth factor. Biochemistry 27: 6675–6681
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Elgjo, K., Reichelt, K.L. Zinc and the mitosis-inhibitory epidermal pentapeptide (EPP) form a stimulatory chelated dimer. Arch Dermatol Res 287, 735–739 (1995). https://doi.org/10.1007/BF01105798
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DOI: https://doi.org/10.1007/BF01105798