What is GHK and Copper Peptide?

Background

Signal peptides stimulate matrix protein production in general and collagen synthesis in specific. They may be accomplished by stimulation and growth of different skin cells like human skin fibroblasts. Signal peptides can also increase elastin, proteoglycan, glycosaminoglycans, and fibronectin proliferation. By increasing matrix cell activities and consequently collagen production, the skin looks firmer and younger. Carrier peptides belong to a general category that acts as a facilitator of an important substance transportation, but their major application is to deliver important trace elements (like copper and manganese) necessary for wound healing and enzymatic processes.

The tripeptide-1 (glycyl-L-histadyl-L-lysine or GHK) is primarily known as carrier peptides. It mainly helps to stabilize and deliver copper. It is also a signal peptide that promotes extra-large collagen aggregates degradation in scars; regular collagen synthesis in normal skin; elastin, proteoglycans, and glycosaminoglycans production; growth rate and migration of different cell types; and antiinflammatory and antioxidant responses.

Introduction

GHK is a tripeptide with the amino acid sequence glycyl-histidyl-lysine. It naturally occurs in human plasma, saliva, and urine. In plasma the level of GHK is about 200 ng/mL (10^-7 M) at age 20, but declines to 80 ng/mL by age 60. This decline in the GHK-level coincides with the noticeable decrease in regenerative capacity of an organism. The human peptide GHK-Cu (copper peptide) was isolated in 1973 by Pickart as an activity in human albumin that caused old human liver tissue to synthesize proteins like younger tissue. Subsequent studies established this activity as a tripeptide with an amino acid sequence glycyl-L-histidyl-L-lysine with a strong affinity for copper that readily formed the complex GHK-Cu. The GHK copper complex (or GHK-Cu) has been proven to exhibit antioxidant, anti-inflammatory, regenerative, and wound healing actions. Recent studies demonstrated that the GHK tripeptide up- and downregulates a large number of human genes, which may contribute to the pleiotropic health promoting effects of its copper complex.

Subsequent studies directed by Borel and Maquart et al. demonstrated that GHK-Cu at a very low, nontoxic concentration (1–10 nanomolar) stimulated both synthesis and breakdown of collagen and glycosaminoglycans. GHK modulated an activity of both metalloproteinases and their inhibitors (TIMP-1 and TIMP-2), acting as a main regulator of wound healing and skin remodeling processes. GHK-Cu stimulated collagen, dermatan sulfate, chondroitin sulfate, and a small proteoglycan, decorin. In 2001 McCormack et al. established that GHK-Cu restored replicative vitality to fibroblasts from patients after anticancer radiation therapy that damages cellular DNA. GHK was also found to attract immune and endothelial cells to the site of an injury.

Function

Wound healing activity of GHK-Cu was confirmed in animal experiments. GHK-Cu accelerated wound healing and increased blood vessel formation and the level of antioxidant enzymes in rabbits. This molecule also induced systemic wound healing in rats, mice, and pigs. It improved the healing of diabetic and ischemic wounds in rats, decreasing the level of TNF-alpha and stimulating collagen synthesis. It also facilitated healing of pad wounds in dogs. Such well-documented skin regeneration activity prompted widespread use of GHK in antiaging cosmetic products.

References:

Gorouhi, Farzam, and Howard I. Maibach. "Topical peptides and proteins for aging skin." Textbook of Aging Skin. Springer Berlin Heidelberg, 2010. 1089-1117.

Pickart, Loren, Jessica Michelle Vasquez-Soltero, and Anna Margolina. "GHK peptide as a natural modulator of multiple cellular pathways in skin regeneration." BioMed research international 2015 (2015).

Pickart, Loren, Jessica Michelle Vasquez-Soltero, and Anna Margolina. "The human tripeptide GHK-Cu in prevention of oxidative stress and degenerative conditions of aging: implications for cognitive health." Oxidative medicine and cellular longevity 2012 (2012).