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Charting calcium-regulated apoptosis pathways using chemical biology: role of calmodulin kinase II by Maria Hägg Olofsson; Mandic Aleksandra Havelka; Slavica Brnjic; Maria C Shoshan; Stig Linder is a scholarly article available to read on EtoBox.

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## Background Intracellular free calcium ([Ca^2+^]~i~) is a key element in apoptotic signaling and a number of calcium-dependent apoptosis pathways have been described. We here used a chemical biology strategy to elucidate the relative importance of such different pathways. ## Results A set of 40 agents ("bioprobes") that induce apoptosis was first identified by screening of a chemical library. Using p53, AP-1, NFAT and NF-κB reporter cell lines, these bioprobes were verified to induce different patterns of signaling. Experiments using the calcium chelator BAPTA-AM showed that Ca^2+^ was involved in induction of apoptosis by the majority of the bioprobes and that Ca^2+^ was in general required several hours into the apoptosis process. Further studies showed that the calmodulin pathway was an important mediator of the apoptotic response. Inhibition of calmodulin kinase II (CaMKII) resulted in more effective inhibition of apoptosis compared to inhibition of calpain, calcineurin/PP2B or DAP kinase. We used one of the bioprobes, the plant alkaloid helenalin, to study the role of CaMKII in apoptosis. Helenalin induced CaMKII, ASK1 and Jun-N-terminal kinase (JNK) activity, and inhibition

Author

Maria Hägg Olofsson; Mandic Aleksandra Havelka; Slavica Brnjic; Maria C Shoshan; Stig Linder

Publisher

BioMed Central; Springer (Biomed Central Ltd.); London: BioMed Central, 2001-; Springer Science and Business Media LLC (ISSN 1472-6769)

Published

2008

Language

EN