GHK-CU (Copper Peptide)

Su J, Zhang Y, Cao Y, Ren T, Zhang K, Chen D, et al.

Biomaterials advances

Researchers covalently grafted GHK-Cu onto injectable, open-hollow nanofibrous poly(gamma-benzyl-L-glutamate) microspheres engineered to mimic the extracellular matrix. In cultured bone-marrow mesenchymal stem cells, the GHK-Cu-functionalized scaffold increased expression of the osteogenic genes Runx2, OPN, and OCN relative to non-functionalized microspheres, and a tube-formation assay showed increased angiogenic activity, supporting a role for the copper complex in osteogenic-angiogenic signaling in this in vitro model.

Hu J, Zhang C, Wang F

European journal of pharmacology

In a zebrafish larvae model, GHK-Cu was applied against copper-sulfate- and lipopolysaccharide-induced acute inflammation. Researchers measured neutrophil and macrophage migration, pro- and anti-inflammatory cytokine expression (tnf-a, il-1beta, il-6, il-10), oxidative-stress markers (nitric oxide, reactive oxygen species, superoxide dismutase activity), and JAK1 pathway signaling. GHK-Cu exposure reduced immune-cell migration and oxidative-stress markers and was associated with downregulation of the JAK1 pathway in this model.

Greco V, Lanza V, Tomasello B, Naletova I, Cairns WRL, Sciuto S, et al.

Bioconjugate chemistry

Using in vitro assays, researchers synthesized copper(II) complexes of hyaluronic-acid-GHK conjugates and examined antioxidant activity and effects on release of osteogenic and angiogenic factors, including BDNF, VEGF, and BMP-2. The copper complex was associated with nuclear translocation of the copper chaperones CCS and Atox1, suggesting a mechanism by which copper-dependent transcriptional activity may support osteogenic and angiogenic factor expression in these models.

Bian Y, Deng M, Liu J, Li J, Zhang Q, Wang Z, et al.

Redox biology

In a mouse model of silica-induced silicosis and in RAW264.7 alveolar-macrophage cell cultures, researchers examined the effect of GHK-Cu on lung inflammation and fibrosis markers, identifying peroxiredoxin 6 (PRDX6) as a binding target. GHK-Cu exposure was associated with reduced oxidative stress in alveolar macrophages and attenuated pulmonary inflammation and fibrosis progression in the silicosis model, without evidence of systemic toxicity reported in the study.

Maquart FX, Pickart L, Laurent M, Gillery P, Monboisse JC, Borel JP

FEBS letters

In cultured human fibroblasts, the tripeptide-copper complex GHK-Cu stimulated collagen synthesis in a concentration-dependent manner, with effects beginning around 10^-12 to 10^-11 M and peaking near 10^-9 M, independent of any change in cell number. The authors noted that a GHK sequence occurs within the alpha-2(I) chain of type I collagen, suggesting the tripeptide could be locally released by proteases at a wound site.