GHK-Cu - Function in Human Body
A number of names have been
used in the scientific literature for GHK.
| Systematic name | N(2)-(N-Glycyl-L-histidyl)-L-lysine |
| CAS Registration number | 49557-75-7 |
| Molecular Formula | C14-H24-N6-O4 |
| General name | Glycyl-histidyl-lysine |
| Synonyms | Copper
glycyl-histidyl-lysine Copper(II)ghk Glycylhistidyllysine Gly-his-lys Iamin NSC 379527 Prezatide (or Prezatide Copper as a complex) |
What is the function of GHK-Cu in the human body? The molecule is present blood plasma, saliva, and urine in physiologically active quantities. Evidence suggests that it is a biochemical feedback signal that is generated after tissue injury. It appears to have two main functions: (1) first as a potent tissue protective, anti-inflammatory agent that limits oxidative damage after tissue injury, and (2) as a signal that activates tissue remodeling, that is, the processes for removal of damaged protein and scar tissue and their replacement by normal tissue. Thus, GHK-Cu links the processes of removal of damaged scar tissue and deposition of new tissue.
GHK, which is generated in damaged tissues, directly accelerates many healing associated properties at concentration of around 10exp(-10)M. Some of the GHK stimulated effects seem to be directly mediated by GHK or GHK-Cu after it obtains copper (II) from albumin. Other actions of GHK and GHK-Cu are likely to arise from GHK-Cu's attraction of wound macrophages and other healing-associated immune cells which, in turn, release families of growth factor proteins appropriate to the repair of the damaged tissue.
Francois Maquart and
colleagues at Reims have argued that GHK-Cu acts on the second phase of healing
as an inducer of tissue remodeling processes. Further support for this concept
is that the molecular weight of collagen fragments induced by GHK-Cu are much
smaller than those produced in the early phase of wound repair. This suggests
that, with the copper complex, collagen synthesis and degradation are
simultaneously occurring. Also, in cell culture, GHK-Cu reduces the secretion of
the scar producing protein, TGF-beta-1 by normal fibroblasts and
keloid-producing fibroblasts. This, combined with GHK-Cu's healing activities,
suggests that scar-free healing needs both, an activation of metalloproteinases,
and a reduction in TGF-beta-1 production.
Proposed Mechanism Copper-Peptide GHK-Cu Actions After Tissue Injury
Information from a variety of sources allows us to propose a mechanism for GHK-Cu effects.The sequence of events of GHK-Cu induced effects appear to be as follows:
1. Initially after tissue damage, the first stage of wound healing processes is activated. These include localized blood coagulation, an early neutrophil invasion that secretes sterilizing oxygen radicals, and later an induction by growth factors, such as TGF-beta-1, of copious amounts of scar-forming collagen to form a protective covering over the injury.
2. A second stage of healing begins to be activated as disrupted cells release proteases that generate a population of peptides that include Gly-His-Lys and His-Gly-His-Lys, both of which have a very high affinity for copper (+2) ion.
3. The Gly-His-Lys and His-Gly-His-Lys begin to accumulate copper (+2) ion from albumin and form GHK-Cu and HGHK-Cu.
4. The accumulation of peptide-bound copper ion produces multiple anti-inflammatory effects that help to stop the actions of sterilizing oxygen radicals and permit the initiation of healing events. GHK-Cu blocks ferritin channels and the release of free (oxidative) iron, thus blocking iron catalyzed lipid peroxidation that occurs after injury. GHK-Cu blocks also interleukin-1 damage to tissue cells.
5. GHK-Cu released into the blood stream raises the body's production of, and circulating blood concentration of, wound macrophages that enhance repair.
6. GHK-Cu suppresses the synthesis of scar development by repressing fibroblast production of TGF-beta-1.
7. GHK-Cu also chemoattracts wound macrophages to the wound area. These macrophages act directly to stimulate healing by removing cellular debris and secreting a family of approximately 20 growth factor proteins.
8. GHK-Cu acts directly on fibroblasts to stimulate m-RNAs for collagen, elastin, proteoglycans, metalloproteinases, and TIMP-1 and TIMP-2. This in turn raises the levels of these proteins. This results in a condition whereby protein synthesis and deposition is occurring concomitant with protein breakdown that removes scar tissue and cellular debris remaining from the tissue disruption. Thus, GHK-Cu links scar reduction and the rebuilding of tissues.
9. GHK-Cu induces angiogenesis by serving as a chemoattractant to direct new blood capillaries to the wound area and by inducing the production of several protein essential for angiogenesis.
10. GHK-Cu induces neuronal outgrowth and re-innervation of the damaged tissues.
11. This mechanism of copper-peptide induced tissue repair appears to function for skin, hair follicles, the stomach lining, the intestinal lining, bone tissue, and hooves and fingernails.
12. This copper-peptide regeneration mechanism is different from most known biochemical hormonal response patterns such as the insulin-glucose system or the erythropoetin-red blood cell system. With these systems, a small change in the concentrations of glucose or red blood cells results in a precisely controlled release of the hormones to re-establish normal glucose or red blood cell levels.
13. The copper-peptide tissue remodeling is a much looser stimulus-response system - somewhat like a "fuzzy logic" response. Traumatic tissue damage is an inherently messy business - damage many be slight or massive. The bodily repair systems do not always receive rapid and clear information as to the extent of tissue damage - damages may be sudden and acute - or the result of a slow degenerative disease. This may explain why dermal scars and lesions last so long in adults; the body just does not recognize the need to remove the imperfections.