Cell death

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Cell death

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Like all living things, the various types of cells in plants, animals, and the many different cell types in humans eventually die. Cell death occurs in one of two ways. Cells can be killed by the effects of physical, biological, or chemical injury. Secondly, in a process that is a normal part of cell biology, cells are induced to kill themselves. Cell suicide is also referred to as apoptosis (from the Greek words apo, meaning from, and ptosis, meaning to fall or to drop).

Cell death is important in disease and the aging process and is also necessary in the development of some fetal organs and tissues.

Cell death that results from injury can be caused by mechanical damage such as tearing, or can be due to physical stresses such as heat. A third-degree sunburn, for example, results in the death of many skin cells. Exposure to toxic chemicals such as acids, corrosive bases, metabolic poisons, and other chemicals is also lethal to many types of cells. For example, excessive consumption of alcohol (ethanol) over time causes death of liver cells in humans. The functioning of the liver becomes progressively impaired. In extreme cases, a liver transplant may be necessary to replace a liver that is so damaged that it ceases to function.

Substances that dehydrate cells can also cause cell death. If the environment outside of a cell contains more salt than the interior of the cell, water flows out of the cell in an attempt to dilute the outside environment. The loss of water can disrupt the functioning of the cell to the point of death. This is called plasmolysis. Conversely, if the interior of a cell is saltier than the exterior environment, water flows into the cell. The cell can swell and burst. This phenomenon is called plasmoptisis.

Some diseases and infections cause chemical cell death. For example, infection of the upper respiratory cells with viruses that causes the common cold kills cells during the viral life cycle.

Causes of chemical or mechanical cell death are varied. Some agents act on the membrane that surrounds cells. The membrane can be dissolved or damaged. Other agents disrupt enzymes that the cell requires to sustain life. Still other agents can disrupt the genetic material inside the cell.

Apoptosis, the process of programmed cell death, is a necessary part of the functioning of an individual cell and, in multi-celled organisms such as humans, of the whole organism. For example, reabsorption of a tadpoles tail during the change from tadpole to frog involves apoptosis. Sloughing of uterine cells in women at the start of menstruation is due to apoptosis of the cells lining the uterine wall. Additionally, apoptosis of extraneous cells during development of a human fetus produces the distinct fingers and toes.

Apoptosis is also important as a means of dealing with threats to an organism. For example, the human immune system contains cells that can stimulate apoptosis of other cells that have been infected with a virus. Similarly, cells with damaged genetic material undergo cell death. Thus, apoptosis helps the entire organism function efficiently by eliminating cells that threaten the whole organism.

Programmed cell death occurs either by the withdrawal of a chemical signal that is required to continue living, or by exposure to a chemical signal that begins the death process. Once stimulated to die, apoptotic cells shrink, develop irregular cell surfaces, and show disintegration of genetic material within their nuclei. Eventually, these cells break into small, membrane-wrapped fragments that are engulfed by nearby cells. The apoptosis process is complex, and involves interactions between numbers of different biochemical compounds. This helps ensure that apoptosis does not initiate by accident, and that the process is limited only to specifically targeted cells.

Molecular biologists Sydney Brenner, Robert Horvitz, and John Sulston were awarded the 2002 Nobel Prize in Physiology or Medicine for their pioneering studies on the genetic regulation of programmed cell death. Their studies, which were carried out in the 1980s using a nematode worm as the model system, has since been shown to have relevance to the process of cell death in humans.

See also Deoxyribonucleic acid (DNA); Eukaryotae.

Resources

BOOKS

Al-Rubeai, Mohamed and Martin Fussenegger, ed. Cell Engineering: Apoptosis. New York: Springer, 2004.

Potten, Christopher and James Wilson. Apoptosis: The Life and Death of Cells. Cambridge: Cambridge University Press, 2004.

PERIODICALS

Wang, J.Y.J. DNA Damage and Apopotosis. Cell Death and Differentiation 8 (November 2001): 10471049.

Zhivotovsky, B. From the Nematode and Mammals Back to the Pine Tree: On the Diversity and Evolution of Programmed Cell Death. Cell Death and Differentiation 9 (September 2002): 86770.

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Cell death

Like all living things, the various types of cells in plants, animals, and the many different cell types in humans must eventually die. Cell death occurs in one of two ways. Cells can be killed by the effects of physical, biological, or chemical injury. Additionally, cells are induced to kill themselves. Cell suicide is also referred to as apoptosis (from the Greek words apo, meaning from, and ptosis, meaning to fall or to drop).

Cell death is important in disease and the aging process. Cellular suicide is also necessary in the fetal development of some organs and tissues.

Cell death that results from injury can be caused by mechanical damage such as tearing, or can be due to physical stresses such as heat . A third-degree sunburn, for example, results in the death of many skin cells. Exposure to toxic chemicals such as acids, corrosive bases, metabolic poisons, and other chemicals is also lethal to many types of cells. Excessive drinking of alcohol (ethanol ) causes death of liver cells in humans.

Substances that dehydrate cells can also cause cell death. If the environment outside of a cell contains more salt than the interior of the cell, water flows out of the cell in an attempt to dilute the outside environment. The loss of water can disrupt the functioning of the cell to the point of death. This is called plasmolysis. Conversely, if the interior of a cell is saltier than the exterior environment, water flows into the cell. The cell can swell and burst. This phenomenon is called plasmoptisis.

Some diseases and infections cause chemical cell death. For example, infection of the upper respiratory cells with viruses that causes the common cold kills cells during the viral life cycle.

Causes of chemical or mechanical cell death are varied. Some agents act on the membrane that surrounds cells. The membrane can be dissolved or damaged. Other agents disrupt enzymes that the cell requires to sustain life. Still other agents can disrupt the genetic material inside the cell.

The process of programmed cell death, apoptosis, or suicide, is a necessary part of the functioning of an individual cell and, in multi-celled organisms such as humans, of the whole organism . For example, reabsorption of a tadpole's tail during the change from tadpole to frog involves apoptosis. Sloughing of uterine cells in women at the start of menstruation is due to apoptosis of the cells lining the uterine wall. Additionally, apoptosis of extraneous cells during development of a human fetus produces the distinct fingers and toes.

Apoptosis is also important as a means of dealing with threats to an organism. For example, the human immune system contains cells that can stimulate apoptosis of other cells that have been infected with a virus . Similarly, cells with damaged genetic material undergo cell death. Thus, apoptosis helps the entire organism function efficiently by eliminating cells that threaten the whole organism.

Programmed cell death occurs either by the withdrawal of a chemical signal that is required to continue living, or by exposure to a chemical signal that begins the death process. Once stimulated to die, apoptotic cells shrink, develop irregular cell surfaces, and show disintegration of genetic material within their nuclei. Eventually, these cells break into small membrane wrapped fragments that are engulfed by nearby cells. The apoptosis process is complex, and involves interactions between numbers of different biochemical compounds. This helps ensure that apoptosis does not initiate by accident, and that the process is limited only to specifically targeted cells.

Molecular biologists Sydney Brenner, Robert Horvitz, and John Sulston were awarded the 2002 Nobel Prize in Physiology or Medicine for their pioneering studies on the genetic regulation of programmed cell death. Their studies, which were carried out in the 1980s using a nematode worm as the model system, has since been shown to have relevance to the process of cell death in humans.

See also Deoxyribonucleic acid (DNA); Eukaryotae.


Resources

periodicals

Wang, J.Y.J. "DNA Damage and Apopotosis." Cell Death and

Differentiation 8 (November 2001): 1047–1049.

Zhivotovsky, B. "From the Nematode and Mammals Back to the Pine Tree: On the Diversity and Evolution of Programmed Cell Death." Cell Death and Differentiation 9 (September 2002): 867–70.

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Cell Death

Cell death is a vital and common occurrence. In humans, some 10 billion new cells may form and an equal number die in a single day. Biologists recognize two general categories of cell death, which include genetically programmed death and death resulting from external forces (necrosis).

Genetically programmed cell death is necessary for replacing cells that are old, worn, or damaged; for sculpting the embryo during development; and for ridding the body of diseased cells. Toward the end of the twentieth century biologists recognized several mechanisms by which cell death could occur. In apoptosis, the most common form of normal cell death, a series of enzyme-mediated events leads to cell dehydration, outward ballooning and rupture of the weakened cell membrane, shrinking and fragmentation of the nucleus, and dissolution of the cell. By a different mechanism some cells generate special enzymes that "cut" cellular components like scissors (known as autoschizis, or "self-cutting"). Damaged cells that will become necrotic may lose the ability to control water transport across the membrane, resulting in swelling from excess fluid intake and disruption of protein structure (oncosis).

Programmed cell death is an important component of embryonic development and eliminates cells that are no longer needed. These include, for example, the cells between what will become fingers, or cells making up the embryo's original fish-like circulatory system as adult blood vessels form. Coordinate processes are called "cell determination," which involves a cell line becoming progressively genetically restricted in its developmental potential. For example, a cell line might become limited to becoming a white blood cell, thus losing the ability to become a liver cell. Cell differentiation occurs when cells take on specific structure and functions that make them visibly different from other cells (e.g., becoming neurons as opposed to liver epithelium).

All life is immortal in the sense that every cell is descendent from a continuous lineage dating back to the first nucleated cells 1.5 billion years ago. Life has been propagated through a repeating process of gamete (egg and sperm) formation by meiotic cell division (which creates genetic diversity by blending maternal and paternal genes), fertilization, and the development of the fertilized egg into a new multicellular organism that produces new gametes.

Can individual cells or cell lines, however, become immortal? This may be possible. HeLa cells (tumor cells from a patient named Henrietta Lack) have been kept alive and dividing in tissue culture for research purposes since 1951. But normal cells have a limit to the number of times they can divide, which is approximately fifty cell divisions (known as the Hayflick limit). The key to cell immortality seems to be the tips of the chromosomes, or telomeres, that protect the ends from degradation or fusion. Telomeres consist of a repeating sequence of DNA nucleotides. They shorten with each replication so that after some fifty divisions replication is no longer possible. An enzyme called "telomerase" adds these sequences to the telomere and extends the Hayflick limit. However, this enzyme is not very abundant in normal cells. When the biologists Andrea G. Bodnar and colleagues introduced cloned telomerase genes into cells, the telomeres were lengthened and the Hayflick limit for the cells greatly extended, suggesting the potential for cellular immortality.

See also: Brain Death; Definitions of Death

Bibliography

Bodnar, Andrea G., et al. "Extension of Life Span by Introduction of Telomerase into Normal Human Cells." Science 279 (1998):349352.

Darzynkiewics, Zbigniew, et al. "Cytometry in Cell Necrobiology: Analysis of Apoptosis and Accidental Cell Death (Necrosis)." Cytometry 27 (1997):120.

Raloff, Janet. "Coming to Terms with Death: Accurate Descriptions of a Cell's Demise May Offer Clues to Diseases and Treatments." Science News 159, no. 24 (2001):378380.

ALFRED R. MARTIN

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cytolysis (sy-tol-i-sis) n. the breakdown of cells, particularly by destruction of their outer membranes.

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cytolysis The breakdown of cells, usually as a result of destruction or dissolution of their outer membranes.

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