Current TopicsThe biology of apoptosis☆
Section snippets
History
The father of modern pathology, Rudolf Virchow, was the first to describe organ injury and disease states as alterations in individual cells.7 Furthermore, in a series of lectures to colleagues at the Institute of Pathology in Berlin in 1858, he described a type of cell death he called “necrobiosis,” which was a result of “spontaneous wearing out of living parts.” In addition, he was clear in defining this type of cell death as differing from necrosis.8 Although it was not considered an
Nuclear changes
Since these initial reports describing apoptosis, there has been further characterization of morphologic events that occur during the apoptotic process. In addition to cellular macroscopic changes, apoptosis also involves nuclear changes. As discussed above, nuclear condensation is a common feature of apoptotic cells. Further examination of the chromatin within apoptotic nuclei has revealed changes in DNA–histone interactions and in the DNA itself. Using a monoclonal antibody to the histone
Apoptosis and disease
Because many disease states involve cell loss or a lack thereof, the study of apoptosis in pathology is crucial to the understanding and eventual treatment of many conditions. The following sections examine apoptosis in major diseases, describe methods of apoptosis detection, and analyze possible therapeutic potential. Because a more thorough review of each is beyond the scope of this review, these topics are covered briefly, with our apologies to the colleagues whose work we have omitted.
Summary
Apoptosis is a complex process that has supported a major research effort in the biomedical sciences. It occurs normally in mammary gland involution and tissue remodeling after lactation131 as well as in the menstrual cycles.132 Apoptotic cells can be seen normally in a number of other organs, such as the eye, intestines, skin, uterus, and between digits during development,27, 30, 133 the so-called degenerations that Glücksmann had discovered nearly 50 years ago.10 Therefore, with the large
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Cited by (83)
Naringenin reduces oxidative stress and necroptosis, apoptosis, and pyroptosis in random-pattern skin flaps by enhancing autophagy
2024, European Journal of PharmacologyPreliminary evidence for the presence of multiple forms of cell death in diabetes cardiomyopathy
2022, Acta Pharmaceutica Sinica BCitation Excerpt :Released cytochrome c combines with apoptosis protease activating factor-1 (APAF-1) to form a complex named “apoptosome” which serves as a platform for the cleavage and activation of downstream caspase-957. In general, regenerative diseases are associated with abnormally decreased apoptosis, whereas degenerative pathological processes are related to abnormally increased apoptosis43–46. For example, over 50% of neoplasms have defects in apoptotic machinery, and HF is characterized by tremendous apoptosis58–61.
A new synthetic resorcinolic lipid 3-Heptyl-3,4,6-trimethoxy-3H- isobenzofuran-1-one: Evaluation of toxicology and ability to potentiate the mutagenic and apoptotic effects of cyclophosphamide
2014, European Journal of Medicinal ChemistryCitation Excerpt :Finally, the phagocyte activity, which is responsible for removing damaged cells or cellular remains from the circulation, seems to be preserved. These conclusions are supported by the histological observations, in which cytoplasm rarefaction and eosinophilia, characteristic apoptotic events [66], were observed only in the livers of the animals that received cyclophosphamide in combination with AMS35AA. These results are supported by the data from the apoptosis assay.
The furano norclerodane diterpenoid disobulbin-D induces apoptosis in normal human liver L-02 cells
2012, Experimental and Toxicologic PathologyCitation Excerpt :Apoptosis is an important mode of cell death that is used to eliminate excess, damaged, or cancerous cells throughout life in a variety of organisms, thus maintaining normal development, tissue remodeling, and homeostasis. It is characterized by several morphological and biochemical changes that include nuclear and cell shrinkage, nuclear fragmentation, DNA fragmentation in a laddering pattern, cytosolic boiling, cell membrane blebbing, poly (ADP-ribose)-polymerase (PARP) cleavage, and fragmentation of the cell into apoptotic bodies following cell death (Geske and Gerschenson, 2001; Loo and Rillema, 1998; Van Gurp et al., 2003). The characteristic changes associated with apoptosis are due to the activation of a family of intracellular cysteine proteases known as caspases, which are synthesized as inactive zymogens.
Poly(ADP-ribose) polymerase-1 (PARP-1) and its therapeutic implications
2010, Vascular PharmacologyCitation Excerpt :One of the essential features of apoptosis is its dependency on ATP for ordered degradation of cellular structures (Hergartner, 2000). Apoptosis is triggered by mild stimuli whereas necrosis is initiated by a severe one (Geske and Gerschenson, 2001). PARP an NAD+ catabolizing enzyme serves as a molecular switch between apoptosis and necrosis.
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Address correspondence and reprint requests to F. Jon Geske, PhD, Department of Pediatrics, National Jewish Medical and Research Center, 1400 Jackson St, Denver, CO 80206.