Apoptosis: a critical process in homeostasis
All cells have a finite lifespan and cell death occurs mainly as a result of passive necrotic processes or due to an active process of programmed cell death termed apoptosis.1,2 Apoptosis plays an important role both in human embryonic development and in 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 and 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.
| Apoptosis | Necrosis |
|---|---|
| Affects single cells | Affects groups of neighboring cells |
| No inflammatory response | Significant inflammatory response |
| Cell shrinkage | Cell swelling |
| Membrane blebbing but integrity maintained | Loss of membrane integrity |
| Increased mitochondria membrane permeability, leading to the release of proapoptotic proteins and subsequent formation of apoptotic bodies | Organelle swelling and lysosmal leakage |
| Chromatin condensation and non-random DNA fragmentation | Random degradation of DNA |
| Apoptotic bodies ingested by neighboring cells | Lysed cells ingested by macrophages |
Figure 1.1. (a) SEM of an apoptotic cell, 5000 x magnification; (b) SEM of a necrotic cell, 5000 x magnification.Click here to view a PDF of this image.
Reprinted from the Purdue CDROM Vol 4, Purdue University with permission. Publisher: J. Paul Robinson. http://www.cyto.purdue.edu/cdroms/flow/vol4/index.htm
Dysregulation of apoptosis is implicated in a variety of diseases states.3 Accelerated cell death is implicated in the pathogenesis of a number of diseases, including neurodegenerative diseases such as Alzheimer's disease and acquired immunodeficiency syndrome (AIDS). Conversely, an inappropriately low rate of apoptosis can give rise to cancer or autoimmune disorders.3
In normal cells, apoptosis is initiated in response to developmental cues, cell stress, changes in growth factor signaling, and signaling from oncogenes. Cancer cells, however, although damaged, are often able to bypass this mechanism and escape apoptosis (Figure 1.2). Dysregulation of apoptosis is a key hallmark of cancer and is critical for cancer development and tumor cell survival.5
Figure 1.2. Critical elements of cancer development.Click here to view a PDF of this image.
Adapted from Hanahan and Weinberg 2000. Reproduced with permission from Cell.