Fig. 11.
Fig. 11. Schematic diagram representing the major processes involved in GW1843-induced apoptosis of Molt-4 cells. GW1843 inhibits the production of thymidine monophosphate (TMP), which is essential to DNA replication, resulting in accumulation of dATP. An uncharacterized signal causes the activation of both acidic pH, Mg2+-independent sphingomyelinase activity (ASMase) and neutral pH, Mg2+-dependent sphingomyelinase activity (NSMase). An increase in intracellular ceramide levels as a consequence of the increased SMase activity causes plasma membrane breakdown and may also activate caspases. The caspase pathway is sensitive to CPP32 inhibition and is characterized by events recognized as hallmarks of apoptosis such as PARP cleavage and DNA laddering.

Schematic diagram representing the major processes involved in GW1843-induced apoptosis of Molt-4 cells. GW1843 inhibits the production of thymidine monophosphate (TMP), which is essential to DNA replication, resulting in accumulation of dATP. An uncharacterized signal causes the activation of both acidic pH, Mg2+-independent sphingomyelinase activity (ASMase) and neutral pH, Mg2+-dependent sphingomyelinase activity (NSMase). An increase in intracellular ceramide levels as a consequence of the increased SMase activity causes plasma membrane breakdown and may also activate caspases. The caspase pathway is sensitive to CPP32 inhibition and is characterized by events recognized as hallmarks of apoptosis such as PARP cleavage and DNA laddering.

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