changes in protein profiles in bortezomib applied multiple myeloma ...

al., 2000). This enzyme is also responsible for the cleavage of important cellular
substrates resulting in the classical biochemical and morphological changes associated
with the apoptotic phenotype. The afore-cited enzyme is activated either in response to
the ligation of cell surface death receptors (extrinsic apoptosis pathways) or in response
to signals originating from inside the cell (intrinsic apoptosis pathways) (Figure 3.2)
(MacFarlane and Williams, 2004).
Figure 3.2. Apoptosis: The Extrinsic and Intrinsic Pathways
(Source: MacFarlane and Williams, 2004)
Apoptotic stimuli (cell injury, the release of certain steroids and growth factor
withdrawal) trigger the release of apoptogenic factors such as cytochrome c (Gewies,
2003). Cytchrome c is an essential protein component of the mitochondrial electron
transport chain that is a loosely bound to the outside of the inner mitochondrial
membrane (Lieberman and Marks, 2009). The intrinsic apoptosis pathway initiates with
the release of it from the inter-mitochondrial membrane space to the cytosol. Once
released, cytochrome c binds to Apoptotic Protease-Activating Factor-1 (APAF-1) and
procaspase-9 which bring about formation of the Apaf1–caspase-9 active complex
called apoptosome and activation of the initiator caspase-9 (Denault and Salvesen,
2002). Then caspase-3 enzyme is activated by the activate caspase-9 (Salvesen and
Renatus, 2002b; Adams, 2003; Danial and Korsmeyer, 2004).
Other apoptosis pathway (extrinsic) activated via death receptor activation by a
ligand (usually a cell surface protein on another cell). Triggering of cell surface death
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