Human skin penetration of a copper tripeptide in vitro as a function of skin layer

Hostýnek, Jurij J.; Dreher, Frank; Maibach, Howard I.

doi:10.1007/s00011-010-0238-9

Cited by 39 publications

(22 citation statements)

References 35 publications

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“…Small metal ions have been shown to penetrate the skin111240414243444546. Our study is the first to show that fine structures within the SC absorb or repel small metal ions.…”

Section: Discussionmentioning

confidence: 57%

The stratum corneum comprises three layers with distinct metal-ion barrier properties

Kubo

Ishizaki

Kawasaki

et al. 2013

Sci Rep

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The stratum corneum (SC), the outermost barrier of mammalian bodies, consists of layers of cornified keratinocytes with intercellular spaces sealed with lipids. The insolubility of the SC has hampered in-depth analysis, and the SC has been considered a homogeneous barrier. Here, we applied time-of-flight secondary ion mass spectrometry to demonstrate that the SC consists of three layers with distinct properties. Arginine, a major component of filaggrin-derived natural moisturizing factors, was concentrated in the middle layer, suggesting that this layer functions in skin hydration. Topical application of metal ions revealed that the outer layer allowed their passive influx and efflux, while the middle and lower layers exhibited distinct barrier properties, depending on the metal tested. Notably, filaggrin deficiency abrogated the lower layer barrier, allowing specific metal ions to permeate viable layers. These findings elucidate the multi-layered barrier function of the SC and its defects in filaggrin-deficient atopic disease patients.

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“…Small metal ions have been shown to penetrate the skin111240414243444546. Our study is the first to show that fine structures within the SC absorb or repel small metal ions.…”

Section: Discussionmentioning

confidence: 57%

The stratum corneum comprises three layers with distinct metal-ion barrier properties

Kubo

Ishizaki

Kawasaki

et al. 2013

Sci Rep

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“…In a similar study, we had observed that Cu‐binding region of LOX‐derived peptides was found to be anti‐angiogenic in both Cu (II) and hypoxia‐mediated angiogenesis . Several Cu‐binding regions in peptides like GHK tripeptide and microplusin are anti‐inflammatory and antimicrobial in function . CTR1‐derived peptides were found to be non‐cytotoxic and inhibited angiogenesis.…”

Section: Discussionmentioning

confidence: 76%

Peptides derived from histidine and methionine‐rich regions of copper transporter 1 exhibit anti‐angiogenic property by chelating extracellular Cu

Narayanan

Natarajan

2017

Chem Biol Drug Des

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Angiogenesis is a process of synthesis of new blood vessels from preexisting vasculature. Copper (Cu) as a micronutrient is important to many proteins for their physiological roles. Cu is transported by ceruloplasmin from liver to other parts of the body. Copper transporter 1 (CTR1) is a transmembrane protein which participate in Cu transport across the cell. It is also known to be involved in angiogenesis. In this study, we have designed three peptides from copper-binding regions of CTR1 which are rich in histidine and methionine. These peptides were screened for their inhibitory effect on angiogenesis in the HUVEC model. Mass spectroscopy studies revealed that all the three peptides derived from CTR 1 (Pep 1, 2, and 3) bound to Cu. The intracellular Cu levels estimated by atomic absorption spectroscopy showed decreased levels of copper in peptide-treated cells as compared to control. These peptides inhibited proliferation, migration, and tube formation in HUVEC by sequestering copper, preventing its entry into the cell and thereby inhibiting angiogenesis.

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“…Copper delivery through the skin has many potential applications and thus is widely studied, including the evaluation of the penetration ability of copper peptides30, biocompatibility of copper containing IUD1, the enhancement of skin absorption through copper-containing nanoparticles10 and microneedle-mediated delivery5. Hence, the safety associated with copper delivery through the skin needs to be established.…”

Section: Discussionmentioning

confidence: 99%

Selected Biomarkers Revealed Potential Skin Toxicity Caused by Certain Copper Compounds

Toh

Tan

et al. 2016

Sci Rep

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Copper is an essential mineral and plays important roles in skin growth and activity. Copper delivery through skin can provide beneficial effects but its potential to induce skin irritation reactions is often overlooked. Data on dermal toxicity caused by copper compounds is scant. Some recognized in vitro skin toxicity methods are unsuitable for all metal compounds. Here, we employ a keratinocyte-based model and evaluated the skin irritation potential of copper compounds at cellular, genomic and proteomic levels. We determined cell viability and cytotoxicity by using tetrazolium reduction assay and Lactate Dehydrogenase (LDH) assay, performed real-time PCR and protein quantification to assess the expression of biomarkers after treating cells with copper peptide (GHK-Cu), copper chloride (CuCl2) and copper acetate (Cu(OAc)2). These copper compounds exhibited different irritancy potentials at the same treatment concentrations. GHK-Cu was not cytotoxic and did not induce any significant change in the expression levels of various skin irritation-related biomarkers. IL-1α and IL-8, HSPA1A and FOSL1 were significantly upregulated following 24-h treatment with CuCl2 and Cu(OAc)2 at 58 and 580 μM without concomitant inhibition in cell viability. GHK-Cu has a low potential of inducing skin irritation and therefore provides a safer alternative for the delivery of copper through skin.

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Human skin penetration of a copper tripeptide in vitro as a function of skin layer

Cited by 39 publications

References 35 publications

The stratum corneum comprises three layers with distinct metal-ion barrier properties

The stratum corneum comprises three layers with distinct metal-ion barrier properties

Peptides derived from histidine and methionine‐rich regions of copper transporter 1 exhibit anti‐angiogenic property by chelating extracellular Cu

Selected Biomarkers Revealed Potential Skin Toxicity Caused by Certain Copper Compounds

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