Cell deaths oncotic

Liu X, Van Vleet T, Schnellmann RG (2004) The role of calpain in oncotic cell death. Annu Rev Pharmacol Toxicol 44 349-370... 

Estacion, M., and Schilling, W.P. 2002. Blockade of maitotoxin-induced oncotic cell death reveals zeiosis. BMC Physiology 2, 2.A... 

All assays require a morphologic study that confirms and differentiates apoptosis from oncotic or other forms of cell death to confirm specificity of the assay. 

Grewal KK, Racz WJ (1993) Intracellular calcium disruption as a secondary event in acetaminophen-induced hepatotoxicity. Can J Physiol Pharmacol 71 26-33 Gujral JS, Knight TR, Earhood A, Bajt ML, Jaeschke H (2002) Mode of cell death after acetaminophen overdose in mice apoptosis or oncotic necrosis Toxicol Sci 67 322-328 Gujral JS, Hinson JA, Earhood A, Jaeschke H (2004) NADPH oxidase-derived oxidant stress is critical for neutrophil cytotoxicity during endotoxemia. Am J Physiol Gastrointest Liver Physiol 287 G243-252... 

Definitive evidence supporting the presence of a receptor would include classic binding studies, which due to scarcity of MTX are difficult to conduct. Nevertheless, if MTX acts like most known nonpeptide marine toxins, one would expect a receptor. For instance, toxins with structural similarities to MTX, like brevetoxins and palytoxin (PTX) have recognized receptors [46-49]. The case of PTX is of particular interest, since it shares some of its cellular effects with MTX, such as membrane depolarization, [Ca i increases and oncotic cell death [50]. 

These findings point out that MTX is a unique tool amongst marine toxins to explore oncotic/ necrotic cell death. 

Gujral JS, Knight TR, Farhood A, Bajt ML, Jaeschke H. 2002. Mode of cell death after acetaminophen overdose in mice Apoptosis or oncotic necrosis Toxicol. Sci. 67(2) 322. 

In all these experimental models, the MTX effect could be divided in three phases (1) a rapidly developing Ca conductance through NSCC (2) uptake of vital dyes (ethidium, YO-PRO and POPO-3) and Fura-2 loss via a cytolitic-oncotic pore (COP) and (3) a secondaiy phase of vital dye uptake and Fura loss in which membrane permeability to larger molecules like LDH enzyme occurs. Fig. 4.4 shows permeability changes in a population study of bovine aortic endothehal cells (BAECs) treated with 0.3 nM MTX. Two phases of ethidium bromide uptake may be observed (steps 2 and 3 of the death process), the second phase correlating in time with LDH release (step 3 of death process). 

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