Programmed cell death Apoptosis

HiBASAMi H, ACHiwA Y, FUJIKAWA T and KOMIYA T (1996) Induction of programmed cell death (apoptosis) in human lymphoid leukemia cells by catechin compounds . Anticancer Res, 16, 1943-46. 

Jilka RL, Weinstein RS, Bellido T, Parfitt AM, Manolagas SC (1998) Osteoblast programmed cell death (apoptosis) modulation by growth factors and cytokines. J Bone Miner Res 13 793-802... 

Regulation of programmed cell death (apoptosis) is not only important in normal cell development and homeostasis [1, 2], but also during the process of carcinogenesis [3], Apoptosis is suppressed in most cancer cells and induction of apoptosis is one cancer treatment strategy [4], There are many processes and factors that can be modulated to induce cancer cell apoptosis, such as regulation of factors involved in cell cycle arrest [5], protein kinase modulation [6], caspase family activation [7], and the balance in expression between Bcl-2 family members [8],... 

Bcl-2 B cell lymphoma protein 2 (Bcl-2) is a family of proteins that regulate apoptosis (programmed cell death). Apoptosis is a necessary process whereby aged or damaged cells are replaced by new cells. Dysfunction of the apoptosis process results in disease inhibition of apoptosis results in cancer, autoimmune disorder, and viral infection, whereas increased apoptosis gives rise to neurodegenerative disorders, myelodysplastic syndromes, ischemic injury, and toxin-induced liver disease. 

In addition to the endoplasmic reticulum, the mitochondria also function as an intracellular calcium reservoir. The mitochondria also play an important role in programmed cell death —apoptosis (see p. 396). 

Sanchez V, Lucas M, Sanz A, Goberna R (1992) Decreased protein kinase C activity is associated with programmed cell death (apoptosis) in freshly isolated rat hepato-cytes. Biosci Rep 12 199-206... 

Figure 14-8. Overview of pathways that regulate programmed cell death. Apoptosis may occur in response to signaling through either the extrinsic pathway or the intrinsic pathway. In each case, proteolytic cleavage activates an initiator caspase, caspase 8 or 9, either of which can cleave an effector caspase such as caspase 3. Apaf-1 is part of a large complex called the apoptosome that mediates the intrinsic pathway. Binding of an extracellular death ligand to its cell-surface receptor activates the extrinsic pathway.

Gl. Garcia-Martinez, V., Macias, D., Ganan, Y, Garcia-Lobo, J. M., Francia, M. V., Fernandez-Teran, M. A., and Hurle, J. M., Intemucleosomal DNA fragmentation and programmed cell death (apoptosis) in the interdigital tissue of the embryonic chick leg bud. J. Cell Set 106, 201-208 (1993). 

Trigger programmed cell death (apoptosis) as opposed to random cell death (necrosis). This allows sub-lethal doses of photosensitiser, preventing damage and inflammatory response in healthy tissue. 

The membrane-associated Akt kinase is now a substrate for protein kinase PDKl that phosphorylates a specific Thr and Ser residue of Akt kinase. The double phosphorylation converts Akt kinase to the active form. It is assumed that the Akt kinase now dissociates from the membrane and phosphorylates cytosolic substrates such as glycogen synthase kinase, 6-phosphofructo-2-kinase and ribosomal protein S6 kinase, p70 . According to this mechanism, Akt kinase regulates central metabolic pathways of the cell. Furthermore, it has a promoting influence on cell division and an inhibitory influence on programmed cell death, apoptosis. A role in apoptosis is suggested by the observation that a component of the apoptotic program. Bad protein (see Chapter 15) has been identified as a substrate of Akt kinase. 

Fig. 1. Proposed mechanism of action of rituximab associated with the apoptosis pathway. Binding of rituximab with the CD20 antigen up-regulates the production of interleukin-10 (IL-10). The IL-10 autocrine loop down-regulates the expression of the bcl-2 protein, which inhibits the intrinsic pathway (or mitochondrial mediated pathway) of apoptosis. The mitochondrial pathway is induced by intracellular stress signals. The translocation of the bcl-2 protein into the mitochondria leads to the activation of caspase 9 via release of cytochrome c and apoptotic protease-activating factor 1. The other pathway, the extrinsic pathway (or death receptor mediated pathway) activates caspase 8. Subsequently, caspase 8 or 9 activates caspase 3, leading to programmed cell death (apoptosis).

Neuronal cell death is required for the development of the nervous system. However, recent studies suggest that neurons die from programmed cell death (apoptosis) in brains deprived of oxygen by stroke [14] and trauma [15], and in the brains of Alzheimer s patients [16], Therefore, prevention of neuronal apoptosis has been considered to be a desirable therapeutic strategy for treating such neurodegenerative diseases, although the value of this approach is not yet evident. We have recently reported that crocin suppresses tumor necrosis factor (TNF)-a-... 

The two guanines are no longer stacked, but the structure is impossible for the trans isomer. The cisplatin adducts appear to prevent proper DNA repair and to induce programmed cell death (apoptosis)/... 

Programmed cell death (apoptosis) is part of many developmental programs and provides for removal of unneeded cells without inflammation... 

The p53 gene product is not the only factor that induces cell cycle arrest or programmed cell death (apoptosis). Two other genes, p73 and p63, encode proteins with transactivation, DNA-binding, and tetramerization domains, and they share considerable homology with p53. Like p53, these proteins also induce cell cycle arrest and apoptosis. Each of these proteins is comprised of several isoforms. The p73 protein is a structural and functional homologue of the p53 protein. 

G. Srkalovic, and A.V. Schally. 1989. Growth inhibition of MXT mammary carcinoma by enhancing programmed cell death (apoptosis) with analogs of LH-RH and somatostatin. Breast Cancer Res. Treat. 14 307-314. 

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