Zinc and the mitosis-inhibitory epidermal pentapeptide (EPP) form a stimulatory chelated dimer

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.