Apoptosis

A form of cell death in which a programmed sequence of events leads to the elimination of cells without releasing harmful substances into the surrounding area. Apoptosis is also called programmed cell death or cell suicide. Apoptosis plays a crucial role in developing and maintaining health by eliminating old cells, unnecessary cells, and unhealthy cells. In contrast to the more familiar messy death known as necrosis, which is caused by an injury or attack that results in the hemorrhaging of cells and inflammation, apoptosis is a neat way to eliminate cells without leaving evidence behind. The human body replaces perhaps a million cells a second. Over the course of a year, that is roughly equal to the number of cells in the human body. Without an orderly process for getting rid of cells, we would double in size within a year. Too little or too much apoptosis plays a role in a great many diseases. When programmed cell death does not work right, cells that should be eliminated may hang around and become immortal. For example, in cancer and leukemia. When apoptosis works overly well, it kills too many cells and inflicts grave tissue damage. This is the case in strokes and neurodegenerative disorders such as Alzheimer, Huntington and Parkinson diseases. A protein called bcl-2 prevents cell suicide in normal healthy cells. Many cancer cells produce bcl-2 in abundance so they are not eliminated, as they should be, by apoptosis. Strictly speaking, the term apoptosis refers only to the structural changes cells go through, and programmed cell death refers to the complete underlying process, but the terms are often used interchangeably. "Apoptosis" is derived from the Greek apo, off, + ptosis, a falling = a falling off or dropping off.

* * *

Programmed cell death; deletion of individual cells by fragmentation into membrane-bound particles, which are phagocytized by other cells. SYN: programmed cell death. [G. a falling or dropping off, fr. apo, off, + ptosis, a falling] Whereas some cells (e.g., cardiac and skeletal muscle fibers, CNS neurons) last a lifetime, others (e.g., epithelial and glandular cells, erythrocytes) have limited life-spans, at the end of which they are genetically programmed to self-destruct, usually to be replaced by others formed by mitosis from surviving cells. Cells in tissue cultures spontaneously undergo a. after about 50 cell divisions. In contrast to cell death caused by injury, infection, or circulatory impairment, a. elicits no inflammatory response in adjacent cells and tissues. Features of a. detectable by histologic and histochemical methods include cell shrinkage, due chiefly to dehydration; increased membrane permeability, with a rise in intracellular calcium and a fall in pH; endonucleolysis (fragmentation of nuclear DNA); and ultimately formation of apoptotic bodies, which are absorbed and removed by macrophages. Besides being due to genetic programming, a. can be induced by injury to cellular DNA, as by irradiation and some cytotoxic agents used to treat cancer. It can be suppressed by naturally occurring factors (e.g., cytokines) and by some drugs (e.g., protease inhibitors). A. typically does not occur in malignant cells. Such cells therefore escape the destiny of their nonmalignant precursor cells and are said to be immortal. Immortalization can occur in various ways. The bcl-2 gene, present in many cancers, directs the production of an enzyme that blocks a. and immortalizes affected cells. Injury to DNA normally triggers a. by activating the p53 tumor suppressor gene, which is missing or mutated in about one-half of all human cancers. Cells that lack this gene can survive chemotherapy and irradiation intended to destroy cancer cells. Failure of a. to occur is also involved in some degenerative diseases, including lupus erythematosus, and may be responsible for cellular damage caused by certain viruses, including HIV.

* * *

apop·to·sis .ap-ə(p)-'tō-sis, -äp-, -ō-; .ā-päp- n a genetically determined process of cell self-destruction that is marked by the fragmentation of nuclear DNA, is activated either by the presence of a stimulus or by the removal of a stimulus or suppressing agent, is a normal physiological process eliminating DNA-damaged, superfluous, or unwanted cells (as immune cells targeted against the self in the development of self-tolerance or larval cells in amphibians undergoing metamorphosis), and when halted (as by genetic mutation) may result in uncontrolled cell growth and tumor formation called also programmed cell death

apop·tot·ic -'tät-ik adj

* * *

n.

programmed cell death, which results in the ordered removal of cells and occurs naturally as part of the normal development, maintenance, and renewal of cells, tissues, and organs. During embryonic development, for example, the fingers are 'sculpted' from the embryonic spadelike hand by apoptosis of the cells between them. Failure of apoptosis has been implicated in the uncontrolled cell division that occurs in cancer. Abnormal apoptosis, due to failure of the mechanisms that control it, may be a causative factor in autoimmune disease.

* * *

ap·op·to·sis (ap″op-toґsis) (ap″o-toґsis) [Gr. “a falling off”] a morphologic pattern of cell death affecting single cells, marked by shrinkage of the cell, condensation of chromatin, formation of cytoplasmic blebs, and fragmentation of the cell into membrane-bound apoptotic bodies that are eliminated by phagocytosis. It is a mechanism for cell deletion in the regulation of cell populations, as of B and T lymphocytes following cytokine depletion. Often used synonymously with programmed cell death (q.v.). apoptotic adj