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Compounds stimulating cytosolic phospholipase A2 activity with a combinational action mode.

Abstract：

:The screening of small synthetic compound libraries is a useful means of identifying molecules that modulate various cellular responses. We screened more than 10,000 different small compounds and identified three synthetic compounds that stimulate arachidonic acid (AA) release in a combinational manner in neutrophil-like differentiated HL60 cells. These three compounds were designated as AARIC-1, -2, and -3, representing AA release inducing compounds-1, -2, and -3. Although AA release was not induced by any single one of these compounds, it was dramatically stimulated by the three compounds in combination. Moreover, the effect of combined treatment by these compounds on AA release was completely abolished by MAFP and AACOCF(3), specific cytosolic phospholipase A(2) inhibitors. Furthermore, we found that AARIC-3 stimulates cytosolic calcium influx, while AARIC-1 induces ERK activation. Taken together, we demonstrate a useful approach to the study of complicated and nonlinear intracellular signaling networks using small synthetic compounds in combination.

journal_name

Biochem Biophys Res Commun

journal_title

Biochemical and biophysical research communications

authors

Bae YS,Park EY,Lee HY,Kang HK,Suh PG,Kwak JY,Ryu SH,Lee T

doi

10.1016/j.bbrc.2004.10.063

subject

Has Abstract

pub_date

2004-12-10 00:00:00

pages

632-8

issue

2

eissn

0006-291X

issn

1090-2104

pii

S0006-291X(04)02366-6

journal_volume

325

pub_type

杂志文章

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