AHK-Cu and Hair Follicle Cell Cultures

AHK-Cu is classified as a tripeptide with the sequence of alanine–histidine–lysine (AHK) which has a copper ion attached to the middle amino acid – histidine. The AHK structure appears to have significant affinity to copper ions (Cu²⁺), mainly due to the imidazole side chain of histidine, apparently acting as the primary anchoring point. Research by Kecel-Gunduza suggests AHK may possibly adopt stable conformations in aqueous conditions, so the result is a stable copper-peptide complex that may act as a “delivery system” for copper ions to cells.⁽¹⁾

In skin cell and hair follicle cell cultures Copper is a cofactor for key enzymes like lysyl oxidase (collagen/elastin crosslinking) and tyrosinase. When bound to AHK, copper may be more bioavailable and directed toward processes like extracellular matrix repair, angiogenesis, and follicle stimulation. Consequently, AHK-Cu might have a role in modulating several processes in endothelial cells, such as hair follicle cells, such as growth, differentiation, and programmed cell death (apoptosis).⁽²⁾⁽³⁾

 

Research

AHK-Cu and Hair Follicle Cell Apoptosis

Based on the research by Pyo et al. AHK-Cu appears to exhibit a concentration-dependent influence on cell survival and proliferation in cultured systems.⁽⁴⁾ The researchers applied the peptide in the picomolar to nanomolar range and observed that it may upregulate the proliferation of dermal papilla cells, a specialized fibroblast population that plays a central role in hair follicular biology. These are posited to act as the main regulatory cells of the hair follicle because they may regulate hair growth and cycling. This proliferative potential was hypothesized by the researchers to be coupled with a shift in the balance of apoptosis-related proteins. Specifically, AHK-Cu might increase the expression of Bcl-2, an anti-apoptotic molecule, while reducing the levels of Bax, a pro-apoptotic counterpart.

The researchers commented that the downstream execution phase of programmed cell death may also be affected by AHK-Cu. Specifically, the researchers suggested that the cleavage of caspase-3 and its substrate called Poly ADP-ribose polymerase (PARP) appeared markedly reduced, by ~43% and ~77% respectively, suggesting that the peptide complex may suppress this cascade of programmed cell death. Caspase-3 is often described as an “executioner” enzyme in the programmed cell death pathway, because once it becomes activated and cleaved, it appears to orchestrate the dismantling of the cell through the proteolytic breakdown of essential structural and regulatory proteins. One of its principal targets is PARP, a nuclear enzyme involved in DNA repair and cellular stress responses. During programmed cell death, cleaved caspase-3 cuts PARP into distinct fragments, effectively halting its repair functions and locking the cell into an irreversible death program. By reducing both the cleavage of caspase-3 itself and the cleavage of PARP, AHK-Cu appears to interfere with this terminal step in the apoptotic process.

The net potential of these molecular events is posited to be an environment more favorable to cell survival, in which proliferative signals outweigh apoptotic triggers. This balance appears to be critical for the maintenance and activity of dermal papilla cells in culture. Pyo et al concluded that their research may have “provided strong in vitro [data] that AHK-Cu may stimulate hair growth by increasing the proliferation of DPCs, and by preventing their apoptosis.” Thus AHK-Cu may act by modulating key checkpoints of the apoptotic machinery while simultaneously encouraging proliferative activity. Through the upregulation of survival pathways and the downregulation of cell death signals, it may create conditions that support cellular persistence and function. Interestingly, the actions of AHK-Cu may follow a narrow window of positive potential, as concentrations above the optimal range may fail to stimulate proliferation and potentially even inhibit cell growth.

AHK-Cu and Collagen Synthesis

Research on AHK-Cu has not been limited to dermal papilla cells. Data also points to its potential influence on other fibroblast populations within the dermis, particularly those deemed responsible for the production and renewal of the extracellular matrix. These fibroblasts are central to maintaining the structural framework of the skin, as they secrete collagen and related matrix proteins that provide tensile strength and resilience.

Experimental work described by Patt et al. suggests that exposing fibroblasts to AHK or its copper complex may lead to measurable increases in both proliferation and cell survival.⁽⁵⁾ Standard viability assays, including those that quantify cell density and metabolic activity, indicated that tested cultures supported higher fibroblast numbers compared to controls. The data suggested that collagen type I synthesis, the predominant form of collagen in connective tissues, rose substantially under the influence of the peptide complex, in some cases reaching several times the baseline production level. Collagen type I is particularly important because it forms the backbone of the extracellular matrix, supporting dermal strength and elasticity. Patt et al. observed that apparently, “AHK-Cu complex stimulates the formation of collagen type I by 300% over the control.” Enhancing its production therefore implies that AHK-Cu might not only support fibroblast persistence in culture but also drive them toward a more active state of matrix renewal.

By promoting both fibroblast proliferation and collagen biosynthesis, AHK-Cu may potentially influence a dual pathway of structural maintenance that involves both sustaining the population of matrix-producing cells while simultaneously accelerating the deposition of new collagen fibers. This dual action may be essential in contexts where dermal integrity is challenged, as a robust extracellular matrix provides not only mechanical support but also biochemical cues necessary for optimal cell function.

AHK-Cu and Angiogenesis

Based on the molecular modeling work described in the research by Kecel-Gunduza, AHK-Cu appears to interact directly with vascular endothelial growth factor receptor 2 (VEGFR-2), a central mediator of angiogenic signaling.⁽¹⁾ The researchers performed docking simulations and suggested that the tripeptide may form stable binding poses with VEGFR-2 through multiple hydrogen bonds, including interactions with residues such as LEU-37, LYS-117, CYS-116, and ASN-120. These interactions apparently produced a meaningful affinity for the receptor’s active region. The significance of this observation lies in the fact that VEGFR-2 activation is one of the primary pathways that regulate endothelial cell proliferation and the growth of new blood vessels. By stabilizing interactions with this receptor, AHK-Cu may help to reinforce pro-angiogenic signaling cascades. In turn, this mechanistic effect might contribute to an environment that favors enhanced nutrient and oxygen delivery through vascularization, complementing the peptide’s other reported influences on cell survival and proliferation. The researchers therefore proposed that the ability of AHK-Cu to interact with VEGFR-2 may represent a key molecular feature underpinning its biological activity on promoting the growth of hair follicle cells and other structures.

NOTE: These products are intended for laboratory research use only. This peptide is not intended for personal use. Please review and adhere to our Terms and Conditions before ordering.

 

References:

1. Kecel-Gunduza S, Kocb E, Bicaka B, Kokcub Y, Ozela AE, Akyuzc S. IN SILICO ANALYSIS FOR CHARACTERIZING THE STRUCTURE AND BINDING PROPERTIES OF ALA-HIS-LYS (AHK) TRIPEPTIDE. The Online Journal of Science and Technology-July. 2020;10(3).
2. Kapoor R, Shome D, Vadera S, Kumar V, Ram MS. QR678 & QR678 Neo Hair Growth Formulations: A Cellular Toxicity & Animal Efficacy Study. Plast Reconstr Surg Glob Open. 2020 Aug 25;8(8):e2843. doi: 10.1097/GOX.0000000000002843. PMID: 32983753; PMCID: PMC7489598.
3. Sadgrove NJ, Simmonds MSJ. Topical and nutricosmetic products for healthy hair and dermal anti-aging using “dual-acting” (2 for 1) plant-based peptides, hormones, and cannabinoids. FASEB Bioadv. 2021 Jun 6;3(8):601-610. doi: 10.1096/fba.2021-00022. PMID: 34377956; PMCID: PMC8332470.
4. Pyo HK, Yoo HG, Won CH, Lee SH, Kang YJ, Eun HC, Cho KH, Kim KH. The effect of the tripeptide-copper complex on human hair growth in vitro. Arch Pharm Res. 2007 Jul;30(7):834-9. PMID: 17703734. https://doi.org/10.1007/BF02978833
5. Patt, L. M., & Procyte, A. (2009). Neova® DNA Repair Factor Nourishing Lotion Stimulates Collagen and Speeds Natural Repair Process. skin, 1, 2.