Involvement of sphingosine-1-phosphate and S1P1 in angiogenesis: analyses using a new S1P1 antagonist of non-sphingosine-1-phosphate analog.
Biochem Pharmacol
; 77(6): 1011-20, 2009 Mar 15.
Article
em En
| MEDLINE
| ID: mdl-19150609
ABSTRACT
Chemical lead 2 (CL2) is the first non-sphingosine-1-phosphate (Sph-1-P) analog type antagonist of endothelial differentiation gene-1 (Edg-1/S1P(1)), which is a member of the Sph-1-P receptor family. CL2 inhibits [(3)H]Sph-1-P/S1P(1) binding and shows concentration-dependent inhibition activity against both intracellular cAMP concentration decrease and cell invasion induced by the Sph-1-P/S1P(1) pathway. It also inhibits normal tube formation in an angiogenesis culture model, indicating that CL2 has anti-angiogenesis activity. This compound improved the disease conditions in two angiogenic models in vivo. It significantly inhibited angiogenesis induced by vascular endothelial growth factor in a rabbit cornea model as well as the swelling of mouse feet in an anti-type II collagen antibody-induced arthritis model. These results indicate that the Sph-1-P/S1P(1) pathway would have an important role in disease-related angiogenesis, especially in the processes of migration/invasion and tube formation. In addition, CL2 would be a powerful tool for the pharmacological study of the mechanisms of the Sph-1-P/S1P(1) pathway in rheumatoid arthritis, diabetes retinopathy, and solid tumor growth processes.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Esfingosina
/
Lisofosfolipídeos
/
Neovascularização Fisiológica
/
Inibidores da Angiogênese
/
Receptores de Lisoesfingolipídeo
Tipo de estudo:
Prognostic_studies
Limite:
Animals
/
Humans
/
Male
Idioma:
En
Revista:
Biochem Pharmacol
Ano de publicação:
2009
Tipo de documento:
Article
País de afiliação:
Japão