Exogenous nitric oxide induces apoptosis in Toxoplasma gondii tachyzoites via a calcium signal transduction pathway.

The mechanism by which nitric oxide (NO)-dependent cytotoxicity acts against Toxoplasma gondii tachyzoites is poorly understood. An NO donor, sodium nitroprusside (SNP), was used to induce death in T. gondii tachyzoites in vitro as a model for investigating (i) whether NO is capable of inducing apoptosis-like death in tachyzoites and (ii) whether a calcium signal transduction pathway is involved. Exposure to 2 mM SNP resulted in a pattern of tachyzoite death that shares many features with metazoan apoptosis and it may involve a calcium signal transduction pathway. Motility and cell survival in these parasites showed a gradual decline with increasing levels of SNP. Features common to metazoan apoptosis are observed after exposure to 2 mM SNP. Ethylene glycol bis-(beta-aminoethyl ether)-N,N,N',N'-tetra-acetic acid (EGTA), Verapamil and bis-(o-aminophenoxy) ethane-N,N,N',N'-tetra-acetic acid/acetoxymethyl ester (BAPTA/AM) partially increased the cell survival concomitant with decreased [Ca2+]i in cells exposed to SNP. An NO scavenger (N-acetylcysteine), the analogue of SNP (devoid of NO), inhibited the rate of apoptosis after SNP treatment compared with SNP treatment without scavenger, but alone did not induce apoptosis. Taken together, the results indicate that SNP is capable of inducing apoptosis in T. gondii tachyzoites via a calcium signal transduction pathway.