Apoptosis is a suicide/evacuation plan that allows living cells to die with dignity, for the good of the organism. Sometimes cells must be broken down and absorbed by the system, without harm to healthy tissue. Apoptosis helps to maintain homeostasis within a biological system. It is the reason we are not born with webbing between our fingers and toes, and an embryonic tail. The mechanisms of apoptosis are carefully regulated within the cell, and can be triggered by stress to the cell or by a developmental signal. Apoptosis has been implicated in the development of many diseases, including cancer, Alzheimer’s, and AIDS.
Healthy adults and children lose billions of cells every day to apoptosis, for a variety of reasons. During fetal development, for example, large numbers of growing neurons attempt to make connections with other nervous system cells. Cells that succeed will survive, and those that do not undergo apoptosis. Otherwise we would be stuck with thousands of useless brain cells. Defective T lymphocytes within the immune system and the cells sloughed off from the uterine lining prior to menstruation are both neutralized by apoptosis.
Once it is triggered, apoptosis is a dynamic process within the cell, and can be induced by stress or by DNA damage by radiation, or side effects from certain anticancer drugs. Apoptosis is a way of eliminating cells that are no longer needed, without the damage that occurs with necrosis, a messier form of cell death that occurs when cells are damaged through trauma or sudden exposure to a toxin. Toxic cell contents can leak out into the surrounding tissue and cause inflammation. Apoptotic cells die in an orderly manner. First they contract, their nuclei condense, bubbles appear on the plasma membrane in a process known as blebbing, and the cell becomes fragmented. These fragments are called apoptotic bodies, and are engulfed by phagocytic cells.
Apoptosis can happen through either an extrinsic pathway or an intrinsic pathway. In the intrinsic pathway cell death is iniated from within the cell, and in the extrinsic pathway apoptosis is triggered through the binding of a pro-apoptotic molecule to a receptor on the surface of the cell. Both pathways lead to caspase activation. Caspases, also known as “executioners,” are proteins that break down structural proteins in the cell, and stimulate DNA fragmentation. Once apoptosis is initiated, phospholipids are exposed on the surface of the cell membrane, a signal to phagocytic cells that the cell has been marked for death. Engulfing cells secrete cytokines to inhibit development of inflammation in surrounding tissues.
Apoptosis is tightly regulated within the cell, and a malfunctioning apoptotic program can lead to disease. Accelerated apoptosis has been implicated in the development of neurodegenerative diseases such as Alzheimer’s. In AIDS patients CD4+ T cells, necessary for an adequate immune response, become apoptotic, whether they are infected by virus or not, through mechanisms that are not yet understood. Cancer cells appear to have an ability to down regulate apoptosis, and therefore grow out of control.
Apoptosis is an important topic in biomedical research, but there is still a long way to go. Researchers want to know what factors trigger apoptosis, and why it sometimes fails. Apoptosis is already a target of manipulation for therapeutic purposes. Intentional activation of apoptosis in cancer cells, for example, has shown promise, and pre-clinical studies are underway. Perhaps this is only the beginning. Understanding the genes that control life and death may offer the hope for better treatment for people suffering from disease and waiting for miracles.
