Apoptotic routes

Sustained cytosolic Ca2+ overload usually results in a different route leading to cell death. It mainly relies on the activation of the calcium/calmodulin (CaM)-dependent phosphatase, calcineurin. Calcineurin-catalyzed dephosphorylation promotes apoptosis by regulating the activity of a number of downstream targets, including the pro-apoptotic Bcl-2 family member, Bad (Wang, et al., 1999), and transcription factors of the NFAT (nuclear factor of activated T cells) family (Rao, et al., 1997). There are also other Ca2+-dependent enzymes contributing to the apoptotic events, and they include several DNA-degrading endonucleases (Robertson, et al., 2000) and Ca2+-activated cystein proteases of the calpain family essential for the enzymatic activation of the crucial pro-apoptotic effectors (Altznauer, et al., 2004). 

Calcineurin. The calcineurin, or Ca2+-calmodulin dependent protein phosphatase (Aramburu et al., 2004) mediates apoptosis through at least two routes. First, this action can be achieved through steroid receptor Nur77 and CD95 ligand this pathway was found in lymphoid cells (Shi et al., 1989). Alternatively, calcineurin dephosphorylates a pro-apoptotic protein Bad (a member of Bcl-2 family), which in turn translocates into mitochondria and triggers release of cytochrome C and activation of caspases (Wang et al., 1999). 

The National Toxicology Program (NTP) has not evaluated uranium compounds in rodent cancer bioassays by any route for the potential to induce cancer in humans. However, because uranium emits predominantly high-LET alpha particles, current theories on gene mutation and apoptotic mechanisms of... 

For this reason, novel molecules are being sought that do not operate exclusively via an apoptotic mechanism, but instead are able to induce cytostatic properties by other routes such as senescence [158]. 

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