Stimulation of sulfated glycosaminoglycan synthesis by the tripeptide-copper complex glycyl-L-histidyl-L-lysine-Cu2+.
Glycyl-L-histidyl-L-lysine-copper (II) complex (GHK-Cu) is a naturally occurring tripeptide with potential healing properties. We studied the effect of GHK-Cu on the synthesis of glycosaminoglycans (GAGs) by normal human fibroblasts in culture. Cells were incubated with 3H glucosamine and 35S sulfate and the radioactivity of isolated GAGs was determined. GHK-Cu induced a dose-dependent increase of the synthesis of total GAGs secreted into the culture medium and those associated with the cell layer. The effect of GHK-Cu was biphasic with a maximal stimulation at 10(-9) to 10(-8) M. At higher concentrations, the rate of synthesis returned progressively to that of control cultures. Electrophoretic analysis of the different GAG populations showed that GHK-Cu preferentially stimulated the synthesis of extracellular dermatan sulfate and cell layer associated heparan sulfate. No influence of GHK-Cu on the synthesis of hyaluronic acid was observed. GHK-Cu stimulation of GAG synthesis may be one of the phenomenons implicated in the wound healing properties of the peptide.
Wegrowski
Y
Y
Laboratoire de Biochimie, CNRS URA 610, UFR de Médicine, Université de Reims Champagne-Ardenne, France.
Maquart
F X
FX
Borel
J P
JP
D000595:Amino Acid Sequence; D002478:Cells, Cultured; D003470:Culture Media; D003871:Dermatan Sulfate / Q000378:metabolism; D004588:Electrophoresis, Cellulose Acetate; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D005944:Glucosamine / Q000378:metabolism; D006025:Glycosaminoglycans / Q000096:biosynthesis* / Q000378:metabolism; D006801:Humans; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000494:pharmacology*; D012867:Skin / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D013268:Stimulation, Chemical; D013462:Sulfur Radioisotopes; D014018:Tissue Distribution; D014316:Tritium
D003470:Culture Media; D006025:Glycosaminoglycans; D009842:Oligopeptides; D013462:Sulfur Radioisotopes; D014316:Tritium; D003871:Dermatan Sulfate; C013786:A73025; C020905:glycyl-histidyl-lysine; D005944:Glucosamine