APOPTOSIS—PROGRAMMED CELL DEATH

The 100 trillion cells of the body are members of a highly organized community in which the total number of cells is regulated not only by controlling the rate of cell division but also by controlling the rate of cell death. When cells are no longer needed or become a threat to the organism, they undergo a suicidal programmed cell death, or apoptosis. This process involves a specific proteolytic cascade that causes the cell to shrink and condense, to disassemble its cytoskeleton, and to alter its cell surface so that a neighboring phagocytic cell, such as a macrophage, can attach to the cell membrane and digest the cell.

In contrast to programmed death, cells that die as a result of an acute injury usually swell and burst due to loss of cell membrane integrity, a process called cell necrosis. Necrotic cells may spill their contents, causing inflammation and injury to neighboring cells. Apoptosis, however, is an orderly cell death that results in disassembly and phagocytosis of the cell before any leakage of its contents occurs, and neighboring cells usually remain healthy.

Apoptosis is initiated by activation of a family of proteases called caspases. These are enzymes that are synthesized and stored in the cell as inactive procaspases. The mechanisms of activation of caspases are complex, but once activated; the enzymes cleave and activate other procaspases, triggering a cascade that rapidly breaks down proteins within the cell. The cell thus dismantles itself, and its remains are rapidly digested by neighboring phagocytic cells.

A tremendous amount of apoptosis occurs in tissues that are being remodeled during development. Even in adult humans, billions of cells die each hour in tissues such as the intestine and bone marrow and are replaced by new cells. Programmed cell death, however, is precisely balanced with the formation of new cells in healthy adults. Otherwise, the body’s tissues would shrink or grow excessively. Recent studies suggest that abnormalities of apoptosis may play a key role in neurodegenerative diseases such as Alzheimer’s disease, as well as in cancer and auto-immune disorders. Some drugs that have been used successfully for chemotherapy appear to induce apoptosis in cancer cells.