Execution phase

Execution Phase Errors (except where stated control is returned to ISIM monitor cannot be continued with a GO)... 

It is now well estahlished that activation of the caspase cascade is an indispensable and sufficient process in the execution phase of apoptosis (Nunez et al, 1998). As for mitochondria-mediated apoptosis, cytochrome c released from the mitochondrial inner membrane is well known to play an important role in the activation of caspase 9, one of the upstream proteases in the cascade (Zou et al, 1997). For activation of caspase 9, cytochrome c or apoptotic protease activating factor 2 (Apaf 2) induces the formation of the complex between Apaf 1 and caspase 9. The resultant activated caspase 9 then activates caspase 3, which in turn leads to the genomic DNA fragmentation and apoptotic cell death. 

Tepper, A.D., Ruurs, P., Wiedmer, T, Sims, PJ., Borst, J. and van Bhtterswijk, W.J., 2000, Sphingomyelin hydrolysis to ceramide during the execution phase of apoptosis results from phospholipid scrambling and alters cell-surface morphology. J. Cell Biol., 150 F5-7. 

The sensitivity to ionizing radiation is maximal in those cells able to activate a co-ordinate program of cell death (apoptosis) primed by the radiation-induced oxidative stress. Albeit apoptosis is a nuclear event and radiation-induced DNA damage is probably the most relevant mechanism of initiation of apoptosis, the control of the execution phase (and sometime also the initiation) takes place at the mitochondrial level. Radioresistance occurs... 

The central dogma of apoptosis is that all the initiating pro-apoptotic stimuli converge on the mitochondrial compartment. Thus, although apoptosis can be initiated elsewhere, the execution phase of apoptosis induced by ionizing radiation needs mitochondria. How do DNA lesions trigger mitochondria Several metabolic pathways coimect mitochondria to the nucleus. 

Changes in mitochondrial stmcture are very relevant during X-ray induced apoptosis. A few hours after irradiation, a hyperpolarisation of A /m is noticed. This likely represents the attempt to restore the depleted ATP levels, stimulating the oxidative burst of surviving mitochondria. If this secondary oxidative stress overcomes the threshold given by mitochondrial thiols, mitochondrial cardiolipin is oxidized and mitochondrial inner membrane allows the leakage of A /m with the consequent initiation of the execution phase. 

The integration process is typically split into two phases. During the first, the design phase, management makes all the fundamental decisions on the orientation of the new company and plans the implementation. This can take two to three months depending on the project s scope and complexity. The second phase, the execution phase, is when the company works out the individual integration actions in concrete terms and implements them. This tends to take one to two years. 

Thus, vhile the value of executing phase studies using svelling methods has been established beyond doubt, the analysis of composition using index-of-refraction data has been disappointing. A different kind of data vhich is useful in the context of the DIT experiment and vhich could serve as an alternative basis for analysis is needed. 

Fig. 5. The execution phase of apoptosis. An apoptotic stimulus causes the release of cytochrome c from mitochondria. The first box contains the components required to activate caspase 9 card refers to the caspase-recruitment domain. Caspase 9 then activates caspase 3 (second box), which in turn activates caspase 6 (last box). The amino-acid sequences at the cleavage sites are shown. Caspases 3 and 6 also have a prodomain that is not present in the active protease in caspase 6 an additional cleavage removes a small portion of the middle of the protein. Various substrates of the caspases are shown, including the pathway by which caspase-activated deoxyribonuclease (CAD) is activated which in turn leads to DNA...

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