Compounds stimulating cytosolic phospholipase A2 activity with a combinational action mode |
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Authors: | Bae Yoe-Sik Park Eun-Young Lee Ha-Young Kang Hyun Kyu Suh Pann-Ghill Kwak Jong-Young Ryu Sung Ho Lee Taehoon |
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Institution: | Medical Research Center for Cancer Molecular Therapy, College of Medicine, Dong-A University, Busan 602-714, Republic of Korea. yoesik@donga.ac.kr |
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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. |
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Keywords: | Phospholipase A2 Small compound Combined treatment Extracellular signal-regulated protein kinase Calcium influx |
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