Glycyl-l-histidyl-l-lysine prevents copper- and zinc-induced protein aggregation and central nervous system cell death in vitro.
Metallomics
; 16(5)2024 05 02.
Article
en En
| MEDLINE
| ID: mdl-38599632
ABSTRACT
Common features of neurodegenerative diseases are oxidative and inflammatory imbalances as well as the misfolding of proteins. An excess of free metal ions can be pathological and contribute to cell death, but only copper and zinc strongly promote protein aggregation. Herein we demonstrate that the endogenous copper-binding tripeptide glycyl-l-histidyl-l-lysine (GHK) has the ability to bind to and reduce copper redox activity and to prevent copper- and zinc-induced cell death in vitro. In addition, GHK prevents copper- and zinc-induced bovine serum albumin aggregation and reverses aggregation through resolubilizing the protein. We further demonstrate the enhanced toxicity of copper during inflammation and the ability of GHK to attenuate this toxicity. Finally, we investigated the effects of copper on enhancing paraquat toxicity and report a protective effect of GHK. We therefore conclude that GHK has potential as a cytoprotective compound with regard to copper and zinc toxicity, with positive effects on protein solubility and aggregation that warrant further investigation in the treatment of neurodegenerative diseases.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Oligopéptidos
/
Zinc
/
Muerte Celular
/
Cobre
/
Agregado de Proteínas
Límite:
Animals
/
Humans
Idioma:
En
Revista:
Metallomics
Asunto de la revista:
BIOQUIMICA
Año:
2024
Tipo del documento:
Article
País de afiliación:
Suecia