The tripeptide GHK, which is made up of the amino acid sequence glycine-histidine-lysine, is reportedly present in all bodily fluids and decreases with age. Studies suggest the fall in GHK levels that comes with aging correlates with the natural slowing of regeneration.
The formation of a copper 2+-complex by GHK is hypothesized to hasten the processes of wound healing and skin restoration. Collagen and glycosaminoglycan production, as well as metalloproteinases and their inhibitors, are all thought to yield results from GHK’s putative multifarious impact. In addition, GHK seems to increase the formation of collagen, dermatan sulfate, chondroitin sulfate, and decorin, possibly renewing fibroblasts after radiation.
The chemical is thought to have chemo-attractive qualities, drawing in immune and endothelial cells to areas of damage to speed up wound healing in many tissues and organs. This includes the skin, hair follicles, digestive system, bone tissue, and canine foot pads. Studies in rats and pigs also suggest that the peptide may stimulate systemic wound healing.
GHK Peptide: Mechanism of Action
Scientists speculate that GHK tripeptide may have a strong affinity for Cu2+ copper ions. It seems that GHK-Cu, which is formed when GHK binds to copper, may be the functional form of the peptide. For many of the hypothetical biological actions of GHK, this copper complex seems to be of paramount importance.
It has been hypothesized that GHK, in both its copper-bound (GHK-Cu) and copper-free forms, may significantly impact the transcription of multiple genes involved in an organism’s response to stress and damage. Tissue remodeling, antioxidant defenses, anti-inflammatory responses, pain modulation, anxiety relief, angiogenesis, neuron outgrowth, and anti-cancer actions are only some of the various biological processes affected by these transcriptional effects. Notably, the GHK sequence is thought to be an essential part of the collagen molecule, and it seems that protein degradation-driven release of GHK and the SPARC protein may occur spontaneously in the wake of injury.
It would seem that copper, a transition metal, is crucial to the functioning of all eukaryotic creatures. The potential of GHK to convert between the oxidized Cu(2+) and reduced Cu(2+) forms suggests that it may play a crucial role in a wide variety of biological activities that rely on electron transfer pathways. A dozen or so enzymes use copper’s redox characteristics to catalyze vital metabolic activities involved in everything from cellular respiration and antioxidant defense to detoxification, blood coagulation, and connective tissue development.
Besides these roles, copper seems to have a crucial role in oxygenation, neurotransmission, embryonic development, and a wide variety of other physiological activities.
GHK Peptide and Cancer
Crucial roles are played by genes involved in caspase activity, growth control, and DNA repair in the setting of cancer suppression.
The aggressive and metastasis-prone features of colon cancer were linked to a collection of 54 genes that were discovered in notable research by Hong et al. in 2010. Using the Connectivity Map at the Broad Institute, researchers looked for substances that could be able to counteract the unique gene expression patterns associated with aggressive cancer characteristics.
The findings of this study provided some fascinating new perspectives. The differential gene expression seen in these cancer-related genes was reversible, and two compounds, GHK and Securinine, seemed to suggest extraordinary capacity to do so.
GHK Peptide and Skin
By using a biodegradable carrier in the form of alginate gel, a recent study suggested that pre-presentation of mesenchymal stem/stromal cells (MSC) with GHK may have resulted in a quantity-dependent increase in the production of proangiogenic factors. Key elements, including vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF), were included in the anticipated increase.
When mesenchymal stem cells (MSC) were pre-given antibodies against integrin alpha 1 and beta 1, a crucial finding appeared. It’s possible that MSC showed a striking inability to stimulate the increased production of VEGF under these conditions.
This convincing discovery suggests that the cellular route regulated by integrins alpha 1 and beta 1 may be intertwined with the action of GHK on the release of trophic substances by MSC.
There is data suggesting that GHK-Cu may increase the stemness and proliferative potential of basal keratinocytes in dermal skin equivalents by upregulating the expression of epidermal stem cell markers like integrins and p63. As a result, GHK’s gene modulatory action may also target the restoration of the gene pattern indicative of healthy stem cells, which in turn may activate cellular pathways, including integrins and p63, to promote skin regeneration.
GHK Peptide and Fibrinogen Production
The fibrinogen molecule is made up of three individual polypeptide chains, designated as alpha, beta, and gamma. It suggests that GHK may have a strong inhibitory impact on the genetic expression of the fibrinogen beta chain (FGB).
Because the synthesis of fibrinogen requires equal amounts of all three polypeptide chains, an inadequacy in FGB is considered to have a significant negative impact on the total fibrinogen manufacturing process.
Interleukin-6 (IL-6) is a key pro-inflammatory cytokine that is a strong positive modulator of fibrinogen production via interactions with fibrinogen genes, and GHK seems to extend its effect to the control of IL-6.
Cellular models suggest that GHK may reduce IL-6 gene expression in SZ95 sebocytes and IL-6 release from skin fibroblasts. Research suggests that when given together, GHK’s twofold impact on the FGB gene and its possible capacity to attenuate IL-6 production indicate systemic inhibition of the fibrinogen synthesis cascade.
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References
[i] Pickart L, Vasquez-Soltero JM, Margolina A. GHK Peptide as a Natural Modulator of Multiple Cellular Pathways in Skin Regeneration. Biomed Res Int. 2015;2015:648108. doi: 10.1155/2015/648108. Epub 2015 Jul 7. PMID: 26236730; PMCID: PMC4508379. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4508379/
[ii] Pickart L, Freedman JH, Loker WJ, Peisach J, Perkins CM, Stenkamp RE, Weinstein B. Growth-modulating plasma tripeptide may function by facilitating copper uptake into cells. Nature. 1980 Dec 25;288(5792):715-7. doi: 10.1038/288715a0. PMID: 7453802. https://pubmed.ncbi.nlm.nih.gov/7453802/
[iii] Pickart L, Vasquez-Soltero JM, Margolina A. GHK and DNA: resetting the human genome to health. Biomed Res Int. 2014;2014:151479. doi: 10.1155/2014/151479. Epub 2014 Sep 11. PMID: 25302294; PMCID: PMC4180391. https://pubmed.ncbi.nlm.nih.gov/25302294/
[iv] Kang YA, Choi HR, Na JI, Huh CH, Kim MJ, Youn SW, Kim KH, Park KC. Copper-GHK increases integrin expression and p63 positivity by keratinocytes. Arch Dermatol Res. 2009 Apr;301(4):301-6. doi: 10.1007/s00403-009-0942-x. Epub 2009 Mar 25. PMID: 19319546. https://pubmed.ncbi.nlm.nih.gov/19319546/
[v] Choi HR, Kang YA, Ryoo SJ, Shin JW, Na JI, Huh CH, Park KC. Stem cell recovering effect of copper-free GHK in skin. J Pept Sci. 2012 Nov;18(11):685-90. doi: 10.1002/psc.2455. Epub 2012 Sep 28. PMID: 23019153. https://pubmed.ncbi.nlm.nih.gov/23019153/
