Part I: The In vitro Effects of a Natural Dipeptide on the Biological Cascade

Jul 1, 2012 | Contact Author | By: Philippe Mondon and Ada Andre - Sederma, France; Karl Lintner, PhD - Sederma and KAL'idees, France
Your message has been sent.
(click to close)
Contact the Author
Save
This item has been saved to your library.
View My Library
(click to close)
Save to My Library
Title: Part I: The In vitro Effects of a Natural Dipeptide on the Biological Cascade
skin elasticityx peptidex fibrillinx LOXx transglutaminasex
  • Article
  • Media
  • Keywords/Abstract
  • Related Material

Keywords: skin elasticity | peptide | fibrillin | LOX | transglutaminase

Abstract: The peptide N-Acetyl-Tyr-Arg-Hexadecylester (NATAH) was found to stimulate the synthesis of tropoelastin in cultured human dermal fibroblasts as well as augment the activity of all important actors in the assembly of elastic fibers, including Fibrillin 1, Fibulin 5, Decorin, LOX and Transglutaminase, among others. This is shown here both in monolayer cell cultures and in a 3D skin model.

View citation for this article

P Mondon, A Andre and K Lintner, Part I: The in vitro effects of a natural dipeptide on the biological cascade, Cosm & Toil 127(7) 510-515 (Jul 2012)

Market Data

  • The global cosmeceuticals market is growing at a rate of 7.7% annually, and is poised to reach $42.4 billion by 2018.
  • While wanting products that have near medical-level results, consumers also still seek green and eco-friendly options.
  • Research and tests backing up products claims are increasingly sought by consumers.
view full article

Excerpt Only This is a shortened version or summary of the article you requested. To view the complete article, please log in or create an account. Registration is Free!

Editor’s note: This article is the first in a two-part series describing the anti-aging effects of a natural dipeptide. The first installment presents in vitro studies; the second considers clinical efficacy.

Peter T. Pugliese, MD, refers to elastin as “the youth protein” and boldly states that “there is probably no single protein that has as much to do with a person’s appearance and well-being as the protein elastin.” The skin’s elasticity and firmness are naturally maintained by a complex system of cross-linked proteins that strengthen the skin’s resistance to stretching. The most important protein structure for maintaining this system is the elastic fiber, which is made up mostly of elastin and associated proteins.

Historic research has indicated that elastin present in skin having undergone actinic elastosis shows changes in its amino acid composition; specifically, in its proportions of tyrosine (Tyr) and arginine (Arg). This, coupled with the fact that fragments of fibrillin-1 and fibulin-5 contain the sequence “Tyr-Arg,” and that triggering the coordinated synthesis of various proteins and enzymes is involved in the production of elastic fibers, led the authors to investigate the potential bioactivity of the natural dipeptide Kyotorphin (Tyr-Arg), albeit modified to N-Acetyl-Tyr-Arg-O-Hexadecyl Ester (NATAH).

The peptide N-Acetyl-Tyr-Arg-Hexadecylester (NATAH) was found to stimulate the synthesis of tropoelastin in cultured human dermal fibroblasts as well as augment the activity of all important actors in the assembly of elastic fibers, including Fibrillin 1, Fibulin 5, Decorin, LOX and Transglutaminase, among others. This is shown here both in monolayer cell cultures and in a 3D skin model.

Excerpt Only This is a shortened version or summary of the article you requested. To view the complete article, please log in or create an account. Registration is Free!

This is an excerpt of an article from GCI Magazine. The full version can be found here.

 

Close

Table 1. Production of elastin and tropoelastin

Table 1. Production of elastin and tropoelastin

Production of elastin and tropoelastin induced by NATAH in NHDF (n = 5 assays)

Table 2. Study of the synthesis of fibrillin-1 induced by NATAH in NHDF

Table 2. Study of the synthesis of fibrillin-1 induced by NATAH in NHDF

The incubation of NHDF with the NATAH peptide resulted in a markedly strong, dose-dependent increase in fibrillin-1 deposition in the cell culture medium, with values approaching those obtained with TGF-β1.

Table 3. The effects of NATAH on both TG and LOXL-1

Table 3. The effects of NATAH on both TG and LOXL-1

The data presented indicates that in normal human skin fibroblasts, NATAH, at the concentration of 12 x 10-6 M/L, increases fibulin-5 synthesis by 59% (p < 0.01) and decorin synthesis by 68% (p < 0.01). These figures compare well with those obtained with TGF- β1 (55%, p < 0.01), the usual positive control.

Figure 1. Schematic of elastic tissue formation mechanisms

Figure 1. Schematic of elastic tissue formation mechanisms

The biological production of the elastic fiber is a complex process involving several players in parallel, resulting in the formation of an effective mature fiber.

Figure 2. N-Acetyl-Tyr-Arg-O-Hexadecyl Ester (NATAH)

Figure 2. N-Acetyl-Tyr-Arg-O-Hexadecyl Ester (NATAH)

The authors investigated the potential bioactivity of the natural dipeptide Kyotorphin (Tyr-Arg), albeit modified to N-Acetyl-Tyr-Arg-O-Hexadecyl Ester (NATAH) for reasons of topical application and improved bioavailability.

Figure 3. Images of elastic fibers in normal human fibroblast culture

Figure 3. Images of elastic fibers in normal human fibroblast culture

Images of elastic fibers in normal human fibroblast culture; a) control and b) with NATAH 9.5 μM/L

Figure 4. Images of the elastic fibers in the reconstructed skin models

Figure 4. Images of the elastic fibers in the reconstructed skin models

Images of the elastic fibers in the reconstructed skin models without (top) and with (bottom) corticoid, a) in the control and b) with NATAH 12 μM/L

Figure 5. Pixel color distribution equivalent to the quantity of elastin

Figure 5. Pixel color distribution equivalent to the quantity of elastin

The results of the analysis showed that the stimulation of elastin was approximately the same in both untreated (+14.6%; p < 0.01) and artificially aged (+14.8%; p < 0.01) skin models exposed to NATAH in comparison with the control skin specimens.

Figure 6. Image of LOXL-1 enzyme synthesis by fluorescence

Figure 6. Image of LOXL-1 enzyme synthesis by fluorescence

Image of LOXL-1 enzyme synthesis by fluorescence a) in control and b) with NATAH 12 μM/L; cell nuclei = orange; LOXL-1 = green

Figure 7. Western blot

Figure 7. Western blot

Western blot of fibulin-5 synthesis by NHDF induced by 12 μM/L NATAH

Footnotes [Mondon 127(7)]

a The Mountains software used for this study is developed by Digitalsurf.

b The Full Thickness Skin model used for this study is manufactured by Phenion.

 

Next image >