Apoptosis: a critical process in homeostasis
All cells have a finite life span and cell death occurs mainly as a result of passive necrotic processes or due to an active process of programmed cell death, or, “apoptosis.”1,2 Apoptosis plays an important role in both human embryonic development and adult tissue homeostasis.2 Apoptosis is the most common mechanism by which the body eliminates damaged or unneeded cells without local inflammation from leakage of cell contents.1,3
Cells that are undergoing apoptosis exhibit a characteristic pattern of morphologic changes, including cell shrinkage, condensation, fragmentation of the nucleus and bubbling of the plasma membrane, known as “blebbing,” and chromatin condensation and nucleosomal fragmentation.4 The resulting membrane-bound apoptotic bodies are consumed by neighboring cells or by macrophages. In contrast, the necrotic mode of cell death represents a passive consequence of mechanical damage or exposure of the cells to toxins. The morphologic differences between — and the physiologic consequences of — apoptosis and passive necrosis are shown in Table 1.1 and Figure 1.1.
Table 1.1 Differential features of apoptosis and necrosis.
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Figure 1.1. (a) SEM of an apoptotic cell, 5000 × magnification; (b) SEM of a necrotic cell, 5000 × magnification. Reprinted from the Purdue CDROM Vol 4, Purdue University with permission. Publisher: J. Paul Robinson.
In normal cells, apoptosis is initiated in response to certain developmental cues, such as a decrease in the local concentration of a particular tissue morphogen or growth factor. Other stimuli include severe stress or damage to vital cellular components, which can be caused by ionizing radiation, heat shock, toxins, cell detachment from surrounding tissue, bacterial or viral infection, and/or oncogenic signaling.5,6
Functional apoptotic pathways are crucial for tissue homeostasis and the dysregulation of apoptosis is implicated in a multitude of disease states. Increased apoptosis pathologically exacerbates many conditions, including acquired immunodeficiency syndrome (AIDS), neurodegenerative disorders such as Alzheimer’s disease and Huntington’s disease, cardiac ischemia, and renal damage.6 Conversely, inadequate apoptosis leads to the development of autoimmune diseases and cancer.3 The malfunction of apoptosis is a key hallmark of cancer and is critical for cancer development and tumor cell survival (Figure 1.2).7 Such health implications underscore the potential of using therapeutic strategies to manipulate apoptosis.6
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Figure 1.2. Critical elements of cancer development.
Adapted from Hanahan and Weinberg, 2000.7 Reproduced with permission from Cell.