Scutellarin targets Wnt5a against zearalenone-induced apoptosis in mouse granulosa cells in vitro and in vivo.
J Hazard Mater
; 464: 132917, 2024 02 15.
Article
en En
| MEDLINE
| ID: mdl-37979429
ABSTRACT
Zearalenone (ZEA) poses severe reproductive toxicity to both humans and animals. Scutellarin has been demonstrated to rescue ZEA-induced apoptosis in mouse ovarian granulosa cells (GCs), but its specific targets remain unclear. In the present study, the potential targets of scutellarin were determined to clarify the mechanisms of scutellarin against ZEA-induced ovarian damage. 287 targets of scutellarin in mouse ovarian GCs were obtained by magnetic nano-probe-based fishing assay and liquid chromatography-tandem mass spectrometry. Wnt5a had the lowest binding free energy with scutellarin at - 8.3 kcal/mol. QRT-PCR and western blot showed that scutellarin significantly increased the Wnt5a and ß-catenin expression compared with the ZEA-treated group, and cleaved-caspase-3 expression was significantly increased in the scutellarin-treated group after interfering with the expression of Wnt5a. The affinity constant (KD) of Wnt5a and scutellarin was 1.7 × 10-5 M. The pull-down assay also demonstrated that scutellarin could specifically bind to Wnt5a protein. Molecular docking results showed that scutellarin could form hydrogen bonds with TRY52, GLN56, and SER90 on Wnt5a protein, and western blot assay confirmed SER90 was an important site for the binding. Scutellarin significantly increased Wnt5a and ß-catenin expression and decreased cleaved-caspase-3 expression in ovarian tissues of mice. In conclusion, scutellarin exerted anti-apoptotic effects on ZEA-induced mouse ovarian GCs by targeting Wnt5a.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Zearalenona
Límite:
Animals
/
Female
/
Humans
Idioma:
En
Revista:
J Hazard Mater
Asunto de la revista:
SAUDE AMBIENTAL
Año:
2024
Tipo del documento:
Article
País de afiliación:
China