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Calcium-dependent guanylate cyclase activator protein
calcium-mediated cell death
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Ionophores are compounds that increase the permeability of cellular membrane barriers to ions by functioning as mobile ion carriers or channel formers. They contain hydrophobic regions conferring lipid solubility and hydrophilic ion-binding regions that delocalise the charge of the ion to shield it from the hydrophobic regions of the membrane lipid bilayer.
Calcium ionophore A23187 is an artificial mobile iron carrier that normally acts as an ion-exchange shuttle molecule transporting one divalent calcium ion into the cell in exchange of two H+. As intracellular calcium levels can be monitored by a variety of fluorescent probes use of A23187 provides information about the involvement of elevated levels of cytosolic free calcium (and indirect information about associated secondary messenger systems) following cytokine receptor mediated signal transduction processes. A postulated participation of calcium in the process under study can be confirmed by employing calcium-specific chelators such as EGTA to produce very low intracellular calcium levels, which should then block the response.
A23187 can cause cell activation, differentiation, or proliferation and thus mimics cellular processes normally observed in response to cytokines. It can be used, therefore, to probe functional capacities of cells and to dissect complex processes into a series of discrete stages at the molecular level. Responses can include production and release cytokines, expression of an early response gene, an oncogene, differentiation antigens, and intracellular adhesion molecules, cell death by apoptosis, progression through the Cell cycle, or inhibition of any of these processes.
Simultaneous treatment of cells with calcium ionophores and other agents (cytokines, drugs, hormones) can be used to investigate whether any of these agents affect (enhance or reverse) any of the elicited responses.
For other agents used to dissect signal transduction pathways mediated by cytokines see: Bryostatins, Calphostin C, Genistein, H8, Herbimycin A, K252a, Lavendustin A, Phorbol esters, Okadaic acid, Staurosporine, Suramin, Tyrphostins, Vanadate.
For other entries pertaining to cell death mechanisms see also the Apoptosis and Cell Death Dictionary section of this encyclopedia.
See REFERENCES for entry Calcium ionophore.
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