[article]
| Titre : |
Multicompartmental protection against toxic glycation late products with a "biobetter" dipeptide |
| Type de document : |
texte imprimé |
| Auteurs : |
Barbara Morand, Auteur ; Christelle Golebiewski, Auteur ; Jessica Guglielmi, Auteur ; Pascale Prouheze, Auteur ; Mélanie Mollet, Auteur ; Patrick Lafitte, Auteur ; Jean-François Nicolaÿ, Auteur ; Mathilde Fréchet, Auteur |
| Année de publication : |
2013 |
| Article en page(s) : |
p. 177-184 |
| Note générale : |
Bibliogr. |
| Langues : |
Anglais (eng) |
| Catégories : |
Composés carbonylés
Glycation
Vieillissement cutané
|
| Index. décimale : |
668.5 Parfums et cosmétiques |
| Résumé : |
Dicarbonyl species such as methylglyoxal and glyoxal are toxic late products (but not end products) of the glycation process that readily react with extracellular matrix proteins and also intracellular cytoplasmic or nuclear targets. These reactive species have thus a major impact on cellular metabolism and actively participate in accelerated skin aging. We designed through a structure-activity relationship study a specific scavenger (DAPHIS) and compared the properties of this compound with those of reference dicarbonyl scavengers and the template antiglycation natural dipeptides carnosine and carcinine. DAPHIS is a bioavailable peptide. It protects the highly sensitive extracellular protein fibrillin-1.
Several in vitro tests highlighted the intra-cellular damage provoked by dicarbonyls. We could show that DAPHIS protects proteins, and in particular type I collagen, from extensive crosslinking by glyoxal or methylglyoxal. It was more efficient than aminoguanidine (a gold standard for dicarbonyl scavenging) and its parent peptides carnosine and carcinine. An ex vivo test with human skin expiants showed that DAPHIS deposited on the surface of human skin expiants limits dicarbonylmediated damage in the dermis.
In human fibroblasts, glyoxal induces the formation of large aggregates of a cytosolic protein, vimentin, which results in a decreased contractile capacity of the fibroblasts (decreased traction on extracellular fibrils). DAPHIS prevented vimentin aggregation and preserved the contractile power of fibroblasts in a dermal equivalent model. This clearly indicated that protection of fibroblasts has a direct effect on preservation of skin mechanical properties.
Final& in the nuclear compartment DA-PHIS could protect dicarbonyl-sensitive histone proteins (both glyoxal and methyl-glyoxal), combating crosslinking and nuclear advanced glycation end product formation. It completely prevented histone damage, while the parent dipeptides carnosine and carcinine had no protective effect and reference scavengers were less effective.
Taken together, these results demonstrate that we have designed a superior dicarbonyl scavenger, a "biobetter" pep-tide, that protects preferential targets of these toxic late products of glycation. Clearly, a high efficiency was required for these sensitive targets, and "regular" scavengers were not suitable. |
| Note de contenu : |
- EXPERIMENTAL : Dicarbonyl scavening assay - eGFP fluorescence assay - eGFP glycation assessment - Collagen crosslinking assay - Ex vivo test on human skin explants exposed to methylglyoxal - Cell proliferation assay - Cytosolic compartment - Nuclear compartment
- RESULTS AND DISCUSSION : Reactivity assessment - Protection of the model protein eGFP - In vitro protection of collagen (extracellular matrix) - Ex vivo protection of extracellular matrix proteins of the dermis - Protection of cutaneous cells - Protection of the intracellular protein vimentin - Protection of nuclear protein histones |
| Permalink : |
https://e-campus.itech.fr/pmb/opac_css/index.php?lvl=notice_display&id=19306 |
in IFSCC MAGAZINE > Vol. 16, N° 3 (07-08-09/2013) . - p. 177-184
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