The Science Behind Our Products

Peptides, Lipopeptides

• Hornebeck W; Moczar E; Szecsi J; Robert L, Fatty acid peptide derivatives as model compounds to protect elastin against degradation by elastases., Biochem Pharmacol 1985 Sep 15;34(18):3315-21

• Offermanns S; Seifert R; Metzger JW; Jung G; Lieberknecht A; Schmidt U; Schultz G

Lipopeptides are effective stimulators of tyrosine phosphorylation in human myeloid cells., Biochem J

1992 Mar 1; 282 ( Pt 2):551-7

• Rasoamanantena P; Moczar E; Robert L; Wei SM; Godeau G; Hornebeck W, Protective effect of oleoyl peptide conjugates against elastolysis by neutrophil elastase and kappa elastin-induced monocyte chemotaxis., Am J Respir Cell Mol Biol 1993 Jan; 8(1):50-5

• McFarland GA; Holliday R.,Retardation of the senescence of cultured human diploid fibroblasts by carnosine., Exp Cell Res 1994 Jun; 212(2):167-75

Abstract

We have examined the effects of the naturally occurring dipeptide carnosine (beta-alanyl-L-histidine) on the growth, morphology, and lifespan of cultured human diploid fibroblasts. With human foreskin cells, HFF-1, and fetal lung cells, MRC-5, we have shown that carnosine at high concentrations (20-50 mM) in standard medium retards senescence and rejuvenates senescent cultures. These late-passage cultures preserve a nonsenescent morphology in the presence of carnosine, in comparison to the senescent morphology first described by Hayflick and Moorhead. Transfer of these late-passage cells in medium containing carnosine to unsupplemented normal medium results in the appearance of the senescent phenotype. The serial subculture of cells in the presence of carnosine does not prevent the Hayflick limit to growth, although the lifespan in population doublings as well as chronological age is often increased. This effect is obscured by the normal variability of human fibroblast lifespans, which we have confirmed. Transfer of cells approaching senescence in normal medium to medium supplemented with carnosine rejuvenates the cells but the extension in lifespan is variable. Neither D-carnosine, (beta-alanyl-D-histidine), homocarnosine, anserine, nor beta-alanine had the same effects as carnosine on human fibroblasts. Carnosine is an antioxidant, but it is more likely that it preserves cellular integrity by its effects on protein metabolism.

• Kamoun A; Landeau JM; Godeau G; Wallach J; Duchesnay A; Pellat B; Hornebeck W., Growth stimulation of human skin fibroblasts by elastin-derived peptides., Cell Adhes Commun 1995 Nov; 3(4):273-81

Abstract

Elastin-derived peptides (kappa-elastin: kappa E, mean molecular mass: 75 kDa), either coated onto plastic dishes or added to culture media (0.26 to 1.33 nM) stimulated the growth of human skin fibroblasts (HSF) strains obtained from different donors and tested at different cell passages (4 to 12). Coated 44.4 micrograms/cm2 insoluble elastin (iE) exhibited the same action; coated iE or kappa E significantly modifies the HSF morphology: after 5-6 days of culture, HSF are more elongated, and at preconfluence state, formation of HSF clusters surrounding iE were observed. Increased 3H thymidine incorporation and proliferative effect of HSF by kappa E (1.3 to 2.2 fold as compared to control cells) was observed after a lag phase period which raised with initial HSF density. Optimal proliferative effect was obtained at kappa E 8.5 10(-10) M, a value close to the dissociation constant (kD = 2.7 10(-10) M) of kappa E to HSF.

Valine-glycine-valine-alanine-proline-glycine (VGVAPG), but not valine-glycine-valine (VGV) or Valine-glycine-valine-valine-glycine-alanine (VGVVGA) also significantly stimulated, optimally at 7.0 10(-10) M, HSF proliferation. It was concluded that the stimulatory influence of elastin derived peptides on HSF proliferation was mediated through a binding to plasmalemmal receptor of HSF.

Peptide Growth Factors and Skin

• Colige A; Nusgens B; Lapiere CM.,Response to epidermal growth factor of skin fibroblasts from donors of varying age is modulated by the extracellular matrix., J Cell Physiol 1990 Dec; 145(3):450-7

Abstract

The present study was undertaken to investigate the effect of epidermal growth factor (EGF) on the biosynthetic activity of skin fibroblasts from donors of varying age and the modulation of their response to this growth factor by culture in a three-dimensional extracellular matrix. When cultured in monolayer on plastic or at the surface of a collagen gel, EGF specifically inhibited collagen synthesis whatever the age of the donor (from 17 to 84 years, n = 11). This inhibition was paralleled by a significant decrease in the steady-state level of procollagen type I mRNAs. When embedded in a three-dimensional floating collagen lattice, EGF stimulated the non-collagen protein (NCP) synthesis in fibroblasts from younger donors (5 out of 6) while fibroblasts from the older ones were not affected. Collagen production by fibroblasts from younger donors was not inhibited as in monolayer (some being even stimulated) while that of the older donors was inhibited as observed in monolayer. The steady-state level of procollagen type I mRNA was not modified by EGF in the three-dimensional culture. No significant difference was observed in the affinity and the number of EGF receptors of the fibroblasts on plastic or embedded in a collagen lattice between young and aged donors. Our results suggest that the environment of the cells can modulate the reactivity to EGF and reveal differences related to in vivo aging.

• Felciani C., Gupta AK, and Sauder, DN, Keratinocytes and cytokine/growth factors, Crit Rev Oral Biol ed, 1996; 7 (4):300-18

• Rambukkana, R., Pistoor, FH., Bos, JD., Kapsenberg, ML., and Das, PK., Effects of contact allergens on human Langerhans cells in skin organ culture: migration, modulation of cell surface molecules, and early expression of interleukin-1 beta protein, Lab Invest. , 1996 Feb; 74(2): 422-436.

• Gilhar, A., Aizen, E., Pillar, T., and Stzioni, A., Effect of donor age on response of skin grafts to gamma-interferon, Dermatology 1995; 191(2): 99-103.

• Jarisch A; Krieg T; Hunzelmann N., Regulation of collagen expression by interleukin-1 beta is dependent on donor age., Acta Derm Venereol 1996 Jul; 76(4):287-90

• Frazier K; Williams S; Kothapalli D; Klapper H; Grotendorst GR., Stimulation of fibroblast cell growth, matrix production, and granulation tissue formation by connective tissue growth factor., J Invest Dermatol 1996 Sep; 107(3):404-11

• Murata H; Zhou L; Ochoa S; Hasan A; Badiavas E; Falanga V., TGF-beta3 stimulates and regulates collagen synthesis through TGF-beta1-dependent and independent mechanisms., J Invest Dermatol 1997 Mar; 108(3):258-62