Cell death apoptotic

In apoptotic cell death, several factors such as growth factors, NO, the tumor suppressor gene p53, and the protein encoded by this gene contribute to the process that leads to cell death. One of the functions of p53 protein is the activation of apoptosis if a cell is transformed to a malignant cell. Apoptosis typically leads to the formation of smaller membrane-encapsulated particles within the cell. Apoptotic cell death begins in the nucleus and proceeds to other parts of the cell. The death process may be quite advanced before it can... 

Fox DA, Campbell ML, Blocker YS. 1997. Functional alterations and apoptotic cell death in the retina following developmental or adult lead exposure. Neurotoxicology 18(3) 645-664. 

Kalariya, NM, Ramana, KV, Srivastava, SK, and van Kuijk, FJ, 2008. Carotenoid derived aldehydes-induced oxidative stress causes apoptotic cell death in human retinal pigment epithelial cells. Exp Eye Res 86, 70-80. 

NO may react with superoxide to yield the highly reactive peroxynitrite, ONOO-. Superoxide may also be converted into H202 and the reactive hydroxyl radical, OH. In this way excessive activation of glutamate receptors leads to oxidative damage. The calcium influx has a major effect on mitochondria and causes them to depolarize and swell. This leads to a pore being formed in the outer mitochondrial membrane, which allows the escape of cytochrome c and procaspases from the mitochondria into the cytosol. Cytochrome c activates the caspase cascade, which leads to apoptotic cell death (Ch. 35). 

Vermes, I., Haanen, C., and Reutelingsperger, C., Flow cytometry of apoptotic cell death, J. Immunol. Methods, 243, 167, 2000. 

Fulleiene derivatives appear to act both in vitro and in vivo by effectively blocking apoptotic cell death in the presence of known chemical, biological and physical toxins, and it would be interesting to evaluate if these derivatives can also block apoptosis occurring during embryonic development. For verification zebiafish embryos were exposed to 1,1-tris, 6 and 7 for 5 days post-fertilization and after staining with acridine orange apoptotic cells were detected. As depicted in Fig. 3.9,1 and 7 showed... 

Figure 3.10 shows the protection of zebrafish embryo hair cells by various water-soluble fullerene derivatives. The data for both gentamicin- and cisplatinum-induced apoptotic cell death are summarized in Table 3.3. Comparing the data for... 

Kim, H.-E., Oh, J. H., Lee, S. K., and Oh, Y. J. (1999c). Ginsenoside Rh2 induces apoptotic cell death in rat C6 glioma via a reactive oxygen- and caspase-dependent but Bcl-XL-inde-pendent pathway. Life Sci. 65, PL33-PL40. 

ENHANCED PEROXIDATION REACTIONS DURING APOPTOTIC CELL DEATH... 

In fact, we found that a-tocopherol, an antioxidant hpid-soluble vitamin, prevented geranylgeranoic acid-induced apoptotic cell death of human hepatoma cells. These results are presented in Figure 1 (Shidoji et al, 1997). 

Figure 1. Inhibition of geranylgeranoic acid-induced apoptotic cell death by a-tocophrol. Increasing concentrations (10 100 pM) of a-tocopherol were added to HuH-7 cell cultures with (closed circle) or without (open circle) 10 pM geranylgeranoic acid. After overnight incubation, the number of the viable cells was counted using a Trypan blue dye exclusion method. Means S.E. (n=3) are shown.

In the literature, most dmg-induced apoptosis is well known to require intracellular hyper-production of reactive oxygen species and several antioxidants inhibit apoptotic cell death. While it is clear that peroxidation reactions induce apoptosis, the precise molecular mechanism of how reactive oxygen species convey death-signals is unknown. 

We directed our initial attention to the mitochondrion-specific phospholipid, cardiolipin because it is particularly rich in polyunsaturated fatty acids which are vulnerable to oxidative attack. It seemed reasonable to speculate that mitochondrial cardiolipin may degrade by the enhanced peroxidation reactions during apoptotic cell death,... 

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. 

In this chapter, we have postulated that cardiolipin may participate in determination of cell fate by allowing cytochrome c release from mitochondrial inner membrane through its peroxidative damage during apoptotic ceU death. And anti-oxidant mitochondrial enzyme, PHGPx may protect cardiolipin from its peroxidation as well as apoptotic cell death. 

Nicholson, D. W., 1999, Caspase stmcture, proteolytic substrates, and function during apoptotic cell death. Cell Death Differ 6 1028-1042. 

Chiarugi A and Moskowitz MA (2002) Cell biology. PARP-1 — a perpetrator of apoptotic cell death Science 297 200-201... 

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