| BIOLOGY: -APOPTOSIS: Cell death |
Investigations into apoptosis have revealed complex interconnections between various cell-death programs, and these networks could affect the treatment of a wide range of diseases.2,3,4,5,6,7,8,9,10 Classification of Cell Death The most widely used classification of mammalian cell death recognizes two types: *apoptosis and * necrosis.3,4,11 * Autophagy, which has been proposed as a third mode of cell death, is a process in which cells generate energy and metabolites by digesting their own organelles and macromolecules.12,13,14,15 Autophagy allows a starving cell, or a cell that is deprived of growth factors, to survive.12,13,14,15 However, cells that do not receive nutrients for extended periods ultimately digest all available substrates and die (autophagy-associated cell death). Distinctions between apoptosis, necrosis, and autophagy entail differences in the mode of death and morphologic, biochemical, and molecular attributes (Figure 1).3,4,11  View larger version (82K): [in this window] [in a new window] Figure 1. Three Pathways of Cell Death. Among the three major pathways of cell death — apoptosis, autophagy, and necrosis — a particular mode of cell death may predominate, depending on the injury and the type of cell. Cross-talk among the different types of cell-death pathways exists at multiple levels and is not shown. Programmed cell death is an important concept. Cell death is "programmed" if it is genetically controlled. Apoptosis and autophagy-associated cell death are the two fundamental types of programmed cell death.3,12 The recognition that cell death can occur by genetically controlled processes has enabled advances in unraveling the mechanisms of many diseases, and this new knowledge has facilitated the development of pharmacologic agents that initiate or inhibit programmed cell death.6,7,8,16 Moreover, there is now evidence that necrosis, traditionally considered an accidental form of cell death, can in certain instances be initiated or modulated by programmed control mechanisms.17,18,19,20,21 Apoptosis Definition Apoptosis is derived from an ancient Greek word that suggests "leaves falling from a tree."22,23,24 In contrast to the swelling of the cell and its organelles that defines necrosis, the principal morphologic feature of apoptosis is shrinkage of the cell and its nucleus (Figure 2 and Figure 3, and Fig. 1 through 4 in the Supplementary Appendix, available with the full text of this article at NEJM.org). The distinction between necrosis and apoptosis is due in part to differences in how the plasma membrane participates in these processes. In necrosis, early loss of integrity of the plasma membrane allows an influx of extracellular ions and fluid, with resultant swelling of the cell and its organelles.17,18,19,20,25,26 In apoptosis, plasma-membrane integrity persists until late in the process. A key feature of apoptosis is cleavage of cytoskeletal proteins by aspartate-specific proteases, which thereby collapses subcellular components.2,5,8,23 Other characteristic features are chromatin condensation, nuclear fragmentation, and the formation of plasma-membrane blebs.  View larger version (106K): [in this window] [in a new window] Figure 2. Apoptotic Cells in Thymus, Liver, and Intestine. Panel A is an electron-microscopical image of a phagocytic cell that has engulfed multiple apoptotic thymocytes. The compacted thymocyte nuclei have a classic crescent-shaped appearance, owing to layering of chromatin along the nuclear membrane (arrows). Normal-appearing nuclei are present at the top and bottom of the field of view (uranyl acetate–lead citrate). The thymic tissue section was obtained from a 26-year-old woman who died after a motor vehicle accident and whose condition was complicated by the acute respiratory distress syndrome and sepsis. Panel B shows a single apoptotic hepatocyte (arrow) containing multiple compacted nuclear fragments indicative of apoptosis (hematoxylin and eosin). The sample was obtained from an 81-year-old man who had been injured in a motor vehicle accident and whose condition was complicated by ventilator-associated pneumonia. Panel C shows two adjacent crypts in colonic mucosa that had immunohistochemical staining for cytokeratin 18 cleavage fragments (brown). Cytokeratin 18 is cleaved by active caspases in both intrinsic and extrinsic apoptotic pathways. Detached cells in crypt lumens and epithelial cells that are still integrated into the crypt lining are positive; these cells also have classic apoptotic nuclear morphology (cytokeratin 18 immunostaining [clone M30] and diaminobenzidine with hematoxylin counterstaining). The tissue sample was obtained from a 24-year-old man who had aortic dissection and bowel ischemia after a motor vehicle accident. Panel D shows colonic intestinal epithelial cells with characteristic apoptotic features of nuclear compaction and fragmentation; the epithelial cells have been sloughed into the bowel lumen (hematoxylin and eosin). The sample was obtained from a 23-year-old patient with ischemic injury to the bowel after intestinal surgery. NEJM. Vol. 361:1570-1583 October 15, 2009 Number 16 Richard S. Hotchkiss, M.D., Andreas Strasser, Ph.D., Jonathan E. McDunn, Ph.D., and Paul E. Swanson, M.D. SEE FULLTEXT http://content.nejm.org/cgi/content/full/361/16/1570 http://www.e-medicum.com/noticiasDelDia/verNoticia.php?noticia=84334 |
 |
 |
 |
NOTICIA SELECCIONADA POR E-MEDICUM |
 |
|
|
Director Médico