Apoptosis
- an introduction
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Apoptosis
- an introduction
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Apoptosis, or programmed cell death, is a normal component of the development and health of multicellular organisms. Cells die in response to a variety of stimuli and during apoptosis they do so in a controlled, regulated fashion. This makes apoptosis distinct from another form of cell death called necrosis in which uncontrolled cell death leads to lysis of cells, inflammatory responses and, potentially, to serious health problems. Apoptosis, by contrast, is a process in which cells play an active role in their own death (which is why apoptosis is often referred to as cell suicide). Upon receiving specific signals instructing the cells to undergo apoptosis a number of distinctive biochemical and morphological changes occur in the cell. A family of proteins known as caspases are typically activated in the early stages of apoptosis. These proteins breakdown or cleave key cellular substrates that are required for normal cellular function including structural proteins in the cytoskeleton and nuclear proteins such as DNA repair enzymes. The caspases can also activate other degradative enzymes such as DNases, which begin to cleave the DNA in the nucleus. The result of these biochemical changes is appearance of morphological changes in the cell. Some of these changes are illustrated in Figure 1, which shows time-lapse microscopy images of a trophoblast cell undergoing apoptosis. Typically, the cytoplasm begins to shrink following the cleavage of lamins
and actin filaments. Nuclear condensation can also be observed following
the breakdown of chromatin and nuclear structural proteins, and in many
cases the nuclei of apoptotic cells take on a "horse-shoe" like
appearance. Cells continue to shrink, packaging themselves into a form
that allows for easy clearance by macrophages. These phagocytic cells
are responsible for removing apoptotic cells from tissues in a clean and
tidy fashion that avoids many of the problems associated with necrotic
cell death. In order to promote their phagocytosis by macrophages, apoptotic
cells often ungergo plasma membrane changes that trigger the macrophage
response. One such change is the translocation of phosphatidylserine from
the inner leaflet of the cell to the outer surface. Membrane changes can
often be observed morphologically through the appearance of membrane blebs
(D) or blisters which often appear towards the end of the apoptotic process.
Small vesicles called apoptotic bodies are also sometimes observed.
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