The Role of Apoptosis in Development, Tissue Homeostasis and Malignancy: Death from inside out
Contents:
More recently it has become clear that PCD can be subdivided into sub-types based on caspase dependence and other criteria Assuncao Guimaraes and Linden, ; Broker et al.
Wyllie, A. H. (Andrew H.)
Autophagic cell death is also observed during development, and is a form of PCD characterized by high levels of autophagy. Highly regulated PCD plays an important role during normal development, such as the sculpting of human brain structure and digits, and the elimination of non-functional cells in the developing and adult immune systems Elmore, PCD in the adult is required for tissue homeostasis , elimination of pathogen-invaded cells, and wound healing. Normal human tissue homeostasis is estimated to involve the PCD of several billion cells per day.
Cancer incidence increases exponentially during aging , making aging the greatest risk factor for cancer. PCD normally plays a critical role as an anti-cancer mechanism Tan et al.
Genetic and biochemical abnormalities within a cell normally trigger PCD, however, cancer cells have typically acquired mutations that allow them to escape or repress apoptosis and survive. Most chemotherapies, including ionizing radiation, function by hyper-stimulating and activating these otherwise repressed PCD pathways. In addition to apoptosis, another critical anti-cancer mechanism is cellular senescence. Cellular senescence is an irreversible cell cycle arrest that can result from telomere erosion, oncogene activation, chromatin abnormalities and other types of damage.
Increasing evidence suggests that senescent cells accumulate during aging and contribute to aging-related loss of function in various adult tissues.
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This accumulation may result from the fact that senescent cells are resistant to apoptosis due to repressed activity of PCD pathway components such as caspase 3 Marcotte et al. The famous tumor-suppressor p53 is mutated in the majority of human cancers, and it suggested that most of the other cancers have mutations in genes in the p53 pathway that result in lack of normal p53 function; therefore loss of normal p53 function appears to be a requirement for most cancers Green and Kroemer, Either way, further cell division is halted, thereby preventing that cell from becoming cancerous.
For example, in mouse, abnormal p53 activity can cause a premature aging-like phenotype, associated with the accumulation of abnormal cells Hinkal et al.
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In both Drosophila and C. Intriguingly, in Drosophila , p53 has been found to have both positive and negative effects on adult life span, depending upon the particular tissue and whether the animal is male or female Shen and Tower, ; Waskar et al. Because p53 is able to regulate PCD, cell senescence, autophagy, mitochondrial metabolism, and other critical cell processes Green and Kroemer, , determining how p53 and autophagy are affecting life span will be an important area for future research.
Increased PCD has been observed for each disease, where it appears to be counterproductive in that cells die that might otherwise continue to support function of the tissue Friedlander, Autophagy is normally involved in the clearance of intracellular inclusions, including protein aggregates, and the increased PCD observed in these diseases is typically autophagic cell death.
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- Dexter, T. Michael [WorldCat Identities];
An increased incidence of apoptosis has been reported for several tissues during aging, even in the absence of overt aging-related disease. For example, aging-associated atrophy of muscle, called sarcopenia in mammals, is observed in organisms ranging from invertebrates to humans. Detailed analysis of sarcopenia in rodents indicates an apoptotic-like mechanism, characterized by mitochondrial changes and caspase-independence Marzetti et al. During aging in Drosophila , apoptotic-like events are observed in both muscle and fat tissue , as indicated by DNA fragmentation assay and caspase activation Zheng et al.
Because normally regulated PCD is required for tissue homeostasis, it seems likely this process will be required for optimal life span, particularly in species like mammals with abundant adult cell turnover.
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In contrast, the ectopic and counterproductive apoptosis associated with tissues that incur damage during aging, such as in sarcopenia, might be expected to limit life span. Similarly, in Drosophila , over-expression of powerful caspase inhibitors such as baculovirus p35 and DIAP1 in the adult animal had no detectable effect on life span Shen et al.
Key topics discussed include genetic control of programmed cell death in development, regulation of cell death in cancer cells, influence of signals, modulators and effectors on cell death and clinical applications. In contrast, necrosis is a more passive cell death mechanism generally characterized by cell swelling. Death from inside out: Key topics discussed include genetic control of programmed cell death in development, regulation of cell death in cancer cells, influence of signals, modulators and effectors on cell death and clinical applications. Each chapter provides good access to other relevant literature for those not familiar with the area. The three organizers are enormously indebted to all the contributors for the enthusiasm with which they delivered their talks, shared in discussion, and finally committed their contributions to these printed pages. Pharm Res 26 7:
However, it remains possible that life span might be limited by caspase-independent PCD mechanisms, perhaps including the apoptotic-like events associated with muscle atrophy, and this will be an interesting area for future research. Epithelial cell growth and differentiation: Papers Book 1 edition published in in English and held by 4 WorldCat member libraries worldwide.
The living haemopoietic microenvironment by Terence D Allen Visual 3 editions published between and in English and held by 3 WorldCat member libraries worldwide "Describes the haemopoietic microenvironments for granulopoiesis and erythropoiesis using time lapse video microscopy, supplemented with conventional light and electron microscopic information The focus is on the mechanisms by which normal and neoplastic cells proliferate, differentiate and undergo apoptosis.
The differentiation of hemopoietic, epithelial and neuronal cells is treated with respect to growth factors, signal transduction, transcription factors, and genes regulating the cell cycle and the commitment to maturation. The role of oncogenes in neoplastic cell growth and cell death is also covered. The book deals with the regulation of globin gene expression by the LCR locus and the mechanisms of RNA stability for iron-binding and other proteins.
The induction of differentiation of neoplastic cells as an alternative approach to cancer therapy is discussed.
Dexter, T. Michael 1945-
Epithelial cell growth and differentiation Book 2 editions published in in English and held by 2 WorldCat member libraries worldwide. The authors are a distinguished international group from a variety of disciplines in biology and medicine and hopefully their articles will convey something of the excitement of this fast-moving field. The three organizers are enormously indebted to all the contributors for the enthusiasm with which they delivered their talks, shared in discussion, and finally committed their contributions to these printed pages.
The Role of Apoptosis in Development, Tissue Homeostasis and Malignancy. Death from inside out. Authors: Dexter, R.M., Wyllie, A.H., Raff, M.C. The Role of Apoptosis in Development, Tissue Homeostasis and Malignancy ( inbunden) a remarkable development of interest in cell death 'from inside out'.
We would also like to acknowledge the gracious way in which the Royal Society hosted the meeting, and in particular Mary Manning for making it the trouble-free and enjoyable experience that it was, and Janet Clifford and Simon Gribbin for skillfully managing the editorial processing of this volume. Block of neuronal apoptosis by a sustained increase of steadystate free.
Wyllie, A. H. (Andrew H.) [WorldCat Identities]
Apoptosis in the haemopoietic system. Programmed cell death and the control of cell survival. The role of the p53 protein in the apoptotic response.