Effects of dihydrotestosterone on adhesion and proliferation via PI3-K/Akt signaling in endothelial progenitor cells.
Endocrine
; 46(3): 634-43, 2014 Aug.
Article
en En
| MEDLINE
| ID: mdl-24190051
The protective effects of male hormones on the cardiovascular system are still in dispute. There is now ample evidence that testosterone level is negatively correlated to the incidence and mortality of cardiovascular disease in men. Endothelial progenitor cells (EPCs) play a vital role in endothelial healing and vascular integrity, which are useful for promoting cardiovascular health. In this study, we investigated the effects of dihydrotestosterone (DHT), a non-aromatizable androgen, on human EPC function and the activation of the phosphatidylinositol-3-kinase (PI3-K)/Akt pathway in vitro. EPCs were incubated with a series of concentrations (1, 10, or 100 nmol/L in DMSO) of DHT for 24 h or with 10 nmol/L DHT for different time (6, 12, 24, 48 h). EPC adhesion and proliferation and the activation of Akt were assayed by cell counting, 5-ethynyl-2'-deoxyuridine incorporation assay, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, and Western blot analysis. Our data demonstrated that DHT significantly increased the proliferative activity and adhesive ability of EPCs in a dose- and time-dependent manner, maximum at 10 nmol/L, 24 h (p < 0.05). Western blot analysis revealed that DHT promoted the phosphorylation of Akt, and the effects of different concentrations of DHT on Akt phosphorylation were consistent with those on EPC proliferation and adhesion (p < 0.05). However, the enhancing effects of DHT on EPCs decreased with administration of the pharmacological PI3-K blocker LY294002 (p < 0.05). In conclusion, DHT can modulate EPC proliferation and adhesion and the PI3-K/Akt pathway plays an important role in this process.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Dihidrotestosterona
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Transducción de Señal
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Adhesión Celular
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Fosfatidilinositol 3-Quinasas
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Células Endoteliales
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Proliferación Celular
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Proteínas Proto-Oncogénicas c-akt
Límite:
Humans
/
Male
Idioma:
En
Revista:
Endocrine
Asunto de la revista:
ENDOCRINOLOGIA
Año:
2014
Tipo del documento:
Article
País de afiliación:
China
Pais de publicación:
Estados Unidos