Stimulation of collagen synthesis in fibroblast cultures by the tripeptide-copper complex Gly-His-Lys-Cu2+

French National Centre for Scientific Research, Lutetia Parisorum, Île-de-France, France
FEBS Letters (Impact Factor: 3.17). 11/1988; 238(2):343-346. DOI: 10.1016/0014-5793(88)80509-X
Source: PubMed


Glycyl-L-histidyl-L-lysine (GHK) is a tripeptide with affinity for copper(II) ions and was isolated from human plasma. This peptide appears to play a physiological role in wound healing. We report the stimulating effect of GHK-Cu on collagen synthesis by fibroblasts. The stimulation began between 10−12 and 10−11 M, maximized at 10−9 M, and was independent of any change in cell number. The presence of a GHK triplet in the α2(I) chain of type I collagen suggests that the tripeptide might be liberated by proteases at the site of a wound and exert in situ healing effects.

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    • "Subsequent studies directed by Maquart et al. (France) demonstrated that GHK-Cu at a very low, nontoxic concentration (1–10 nanomolar) stimulated both the synthesis and breakdown of collagen and glycosaminoglycans [55, 56]. It modulated an expression of both metalloproteinases and their inhibitors (TIMP-1 and TIMP-2), improving wound healing and facilitating skin remodeling processes [57]. "
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    ABSTRACT: Oxidative stress, disrupted copper homeostasis, and neuroinflammation due to overproduction of proinflammatory cytokines are considered leading causative factors in development of age-associated neurodegenerative conditions. Recently, a new mechanism of aging-detrimental epigenetic modifications-has emerged. Thus, compounds that possess antioxidant, anti-inflammatory activity as well as compounds capable of restoring copper balance and proper gene functioning may be able to prevent age-associated cognitive decline and ward off many common neurodegenerative conditions. The aim of this paper is to bring attention to a compound with a long history of safe use in wound healing and antiaging skin care. The human tripeptide GHK was discovered in 1973 as an activity in human albumin that caused old human liver tissue to synthesize proteins like younger tissue. It has high affinity for copper ions and easily forms a copper complex or GHK-Cu. In addition, GHK possesses a plethora of other regenerative and protective actions including antioxidant, anti-inflammatory, and wound healing properties. Recent studies revealed its ability to up- and downregulate a large number of human genes including those that are critical for neuronal development and maintenance. We propose GHK tripeptide as a possible therapeutic agent against age-associated neurodegeneration and cognitive decline.
    Oxidative Medicine and Cellular Longevity 05/2012; 2012(3):324832. DOI:10.1155/2012/324832 · 3.36 Impact Factor
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    • "The following are characteristic of ECM remodelling that can contribute to stiffness and systolic/diastolic failure: total collagen content, collagen subtypes, collagen protein stability, collagen cross-linking (Iimoto et al., 1988; Jalil et al., 1989; Mukherjee & Sen 1990; Norton et al., 1997). The activation of MMPs involves collagen degradation with replacement of fibrotic tissue (Dollery et al., 1995; Li et al., 2000b; Maquart et al., 1988). "
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    ABSTRACT: Thesis (Ph. D.)--University of Southern California, 1991. Includes bibliographical references (leaves 93-94).
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