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Effect of PPADS on achondroplasic chondrocytes: inhibition of FGF receptor type 3 over-activity.

Abstract：

:Achondroplasia, results from a mutation in the FGF receptor type 3, leading to receptor hyperactivation and subsequent amplification of FGF receptor type 3 signals. We have tested the ability of pyridoxal-5'-phosphate-6-azophenyl-2', 4'-disulfonate (PPADS) to decrease the overactivation and signalling of FGF receptor type 3 in achondroplasic chondrocytes. PPADS reduced the tyrosine phosphorylation of FGF receptor type 3 triggered by fibroblast growth factor 9 (FGF9) (50% reduction), as well as the activation of extracellular signal-regulated kinases 1 and 2 (ERK1/2) pathway. As a consequence of this inhibitory effect on ERK1/2 activity the loss of extracellular matrix was also reversed by PPADS. The action of PPADS seems to be due to a mechanism independent of P2 receptor antagonism.

journal_name

Eur J Pharmacol

journal_title

European journal of pharmacology

authors

Guzmán-Aránguez A,Crooke A,Yayon A,Pintor J

doi

10.1016/j.ejphar.2008.02.002

subject

Has Abstract

pub_date

2008-04-14 00:00:00

pages

72-7

issue

1

eissn

0014-2999

issn

1879-0712

pii

S0014-2999(08)00149-0

journal_volume

584

pub_type

杂志文章

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