Apoptosis death

M5. Martin, S. J., and Green, D. R., Protease activation dtrring apoptosis Death by a thousand cuts Cell 82, 349-352 (1995). 

Mechanosensing is used to describe the process by which cells sense mechanical forces. Mechanochemical transduction is the phrase that is used to try to describe the biological processes by which external forces such as gravity influence the biochemical and genetic responses of cells and tissues. Specifically, these responses include stimulation of cell proliferation or apoptosis (death) and synthesis or catabolism of components of the extracellular matrix. These processes cause either increases in chemical energy (conversion of amino acids or other small molecules into macromolecules) or decreases in chemical energy (depolymerization of macromolecules). 

Caspase-8 FLICE, MACH, Mch5 Caspase-3, caspase-4, caspase-6, caspase-7, caspase-9, caspase-10, caspase-13, PARP, Bid Apoptosis (death receptors)... 

Wyllie, A. H. (1994) Apoptosis death gets a break. Nature 369, 272-273. 

Hengartner, M. (1998) Apoptosis. Death by crowd control. Science, 281, 1298-1299. 

Vimses cause a range of structural and biochemical effects (cytopathic effects) on the host cells. Most virus infections cause alterations to cell surface membranes, cell lysis, and apoptosis (death to the host cell), though some viruses result in no apparent changes to the infected cells [7]. Hundreds of human-infecting viruses have been clinically investigated, but the majority of natural antiviral extracts were tested against human immunodeficiency virus (HIV), herpes simplex viruses (HSV), rhinoviruses, enteroviruses, hepatitis (Hep), and influenza viruses. 

Martin SJ, Greai DR (1995) Protease activation during apoptosis death by a thousand cuts . Cell 82 349... 

Effect of Impurities Another important factor is the influence of impurities included in CNTs, especially iron that is used as a catalyst during CNT fabrication. In fact, the carcinogenic power of asbestos is increased by iron, which accelerates the generation of oxygen radical species. It has been generally agreed that f-CNTs represent a major improvement over unmodified, non-functionalized (pristine) CNTs. It has been found that pristine CNTs show toxicity on cell lines and causes necrosis and apoptosis deaths even after purification [37]. 

NO made by hematopoietic cells and by non-hematopoietic cells can modulate the differentiation and survival of normal and leukemic blood cells. Depending on the source of NO (extrinsic versus intrinsic to the cell), the rate of production/delivery, the concentration, and most Ukely the specific target cell, NO can either mediate cytotoxicity (stasis, lysis, apoptosis, death) or cytoprotection. Treatments aimed at directing delivery of high-dose NO to leukemia cells using cell type-specific NO pro-drugs may be useful in the treatment of certain leukemias. Likewise, certain NOS inhibitors reproducibly induce apoptosis and death of leukemia cells, and these drugs may be useful in the treatment of certain leukemias. 

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... 

Bursch, W. Oberhammer, F., and Schulte-Herrnann, R. (1992). Cell death by apoptosis and its protective role against di.sease. Trends Pharmacol. Set. 1.3(6), 245-251. 

Active caspases 8, 9 and 10 can convert caspase-3, the most abundant effector caspase from its pro-form to its active cleaved form. Cleavage of a number of different substrates by caspase-3 and also by caspase-6 and -7 which are two other executioner caspases besides caspase-3 then results in the typical morphology which is characteristic of apoptosis. Yet, the activation of caspase-3 and also of caspase-9 can be counteracted by IAPs, so called inhibitor of apoptosis proteins. However, concomitantly with cytochrome C also other proteins are released from mitochondria, including Smac/DIABLO. Smac/DIABLO and potentially other factors can interact with IAPs and thereby neutralize their caspase-inhibitory activity. This releases the breaks on the cell death program and allows apoptosis to ensue. 

There is also crosstalk between the two pathways above the mitochondria. The BH3-only protein BID is cleaved by caspase-8 and -10 which yields truncated BID (tBED), the active pro-apoptotic fragment of BID. Thereby, even in cells in which the direct apoptosis pathway which result from death receptor crosslinking is blocked, e.g. by high expression levels ofthex-linked IAP (XIAP), the activity of tBED on mitochondria can result in the activation of caspase-3 because the IAP-imposed block on full caspase-3 activation and caspase-9 activity at the apoptosome is released by Smac/ DIABLO. 

A substantial amount of indirect evidence supports the contention that the induction of apoptosis in tumor cells is critical to successful therapy. Cancer therapy might therefore be viewed as an attempt to induce apoptosis in a population of cells that have undergone selection for apoptotic defects. If correct, this hypothesis would suggest why cancer therapy is in many cases unsuccessful. However, recent studies indicate that this fundamental problem can be circumvented. Progress in the identification of molecules key to the cell death pathways has led to a growing understanding of how apoptosis occurs [3]. It has become clear that pathways to apoptosis are numerous and often interconnected. A solution to the clinical problem of therapeutic resistance, then, may lie in the fact that there appears to be multiple ways that a cell death program can be implemented. 

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