Cellular non-heme iron modulates apoptosis and caspase 3 activity

Caspases are a family of cysteine proteases that play an essential role in the signaling cascade leading to apoptosis. There is a considerable body of literature indicating that NO, produced either extracellularly by low-molecular-weight S-nitrosothiols (LMW RSNOs) or endogenously by nitric oxide synthase (NOS) prevents caspase 3-dependent apoptosis in various cell types. These effects were suggested to reflect the S-nitrosation of caspase 3 and procaspase 9, respectively. Current research on caspases includes attempts to impede the action of these proteases in order to better understand the apoptotic pathways, as well as to develop drugs that can regulate apoptosis. Observations that NO impedes caspases and apoptosis provided a foundation for the synthesis of prodrugs that could be used for liver-specific delivery of NO.