More than One Way to Die: Apoptosis, Necrosis and Reactive Oxygen Damage

Department of Molecular Biology, University of Ghent, K.L. Ledeganckstraat 35, B-9000 Ghent, Belgium.
Oncogene (Impact Factor: 8.46). 12/1999; 18(54):7719-30. DOI: 10.1038/sj.onc.1203249
Source: PubMed

ABSTRACT Cell death is an essential phenomenon in normal development and homeostasis, but also plays a crucial role in various pathologies. Our understanding of the molecular mechanisms involved has increased exponentially, although it is still far from complete. The morphological features of a cell dying either by apoptosis or by necrosis are remarkably conserved for quite different cell types derived from lower or higher organisms. At the molecular level, several gene products play a similar, crucial role in a major cell death pathway in a worm and in man. However, one should not oversimplify. It is now evident that there are multiple pathways leading to cell death, and some cells may have the required components for one pathway, but not for another, or contain endogenous inhibitors which preclude a particular pathway. Furthermore, different pathways can co-exist in the same cell and are switched on by specific stimuli. Apoptotic cell death, reported to be non-inflammatory, and necrotic cell death, which may be inflammatory, are two extremes, while the real situation is usually more complex. We here review the distinguishing features of the various cell death pathways: caspases (cysteine proteases cleaving after particular aspartate residues), mitochondria and/or reactive oxygen species are often, but not always, key components. As these various caspase-dependent and caspase-independent cell death pathways are becoming better characterized, we may learn to differentiate them, fill in the many gaps in our understanding, and perhaps exploit the knowledge acquired for clinical benefit.

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Available from: Rudi Beyaert, Aug 04, 2014
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    • "Autophagy is an evolutionarily conserved catabolic type of cell death where cytoplasmic macromolecules and organelles are sequestered within double-membraned vacuoles or autophagosomes and finally digested by lysosomal hydrolases, while necrosis involves cell swelling, organelle dysfunction and cell lysis (Mizushima 2004; Klionsky et al. 2008; Kroemer et al. 2009). The mechanism by which a cell dies depends in part on the tissue type or cell, the developmental stage of the tissue, the physiologic environment and the nature of the cell death signal (Fiers et al. 1999; Zeiss 2003). A range of synthesized mono-dentate phosphine complexes was investigated as potential agents to induce cell death in MCF-7 breast cancer cells. "
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    • "Cell death triggered by defined biochemical pathways plays critical roles in normal tissue development as well as in diverse pathological processes (Fiers et al., 1999). Apoptosis and necrosis constitute the two major forms of cell death caused by these pathways, and are characterized by distinct morphological and biochemical alterations. "
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    • "It seems that probably these mechanisms together contribute to ethanol-induced damage. There are several reports that NTFs influence the expression and/or stability of protective antioxidant enzymes (Guegan et al., 1999; Mattson et al., 1995; Sampath et al., 1994), whereas NTF levels reduction can induce reactive oxygen species (Fiers et al., 1999; Schulz et al., 1997). Thus, reductions in such neurotrophic support, in addition to depriving developing neuronal populations of substances essential to their maintenance, could also trigger secondary events that would be further damaging. "
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