Regulated Cell Death Apoptosis

It is obvious that the proliferation and differentiation of cells are important for the development and maintenance of homeostasis in multicellular organisms. Only recently, however, have physiologists come to appreciate the contribution of another characteristic shared by virtually all cells—the ability to self-destruct by activation of an intrinsic cell suicide program. This type of cell death, termed apoptosis, plays important roles in the sculpting of a developing organism and in the elimination of undesirable cells (for example, cells that have become cancerous), but it is particularly crucial for regulating the number of cells in a tissue or organ. Thus, the control of cell number within each cell lineage is normally determined by a balance between cell proliferation and cell death, both of which are regulated processes. For example, white blood cells called neutrophils are programmed to die by apoptosis 24 hours after they are produced in the bone marrow.

Vander et al.: Human Physiology: The Mechanism of Body Function, Eighth Edition

Homeostatic Mechanisms and Cellular Communication CHAPTER SEVEN

Apoptosis occurs by controlled autodigestion of the cell contents. Within a cell, endogenous enzymes are activated that break down the cell nucleus and its DNA, as well as other cell organelles. Importantly, the plasma membrane is maintained as the cell dies so that the cell contents are not dispersed. Instead the apop-totic cell sends out chemical messengers that attract neighboring phagocytic cells (cells that "eat" matter or other cells), which engulf and digest the dying or dead cell. In this way the leakage of breakdown products, many of which are toxic, from apoptotic cells is prevented. Apoptosis is, therefore, very different from the death of a cell due to externally imposed injury; in that case (termed necrosis) the plasma membrane is disrupted, and the cell swells and releases its cytoplasmic material, inducing an inflammatory response, as described in Chapter 20.

The fact that virtually all normal cells contain the enzymes capable of carrying out apoptosis means that these enzymes must normally remain inactive if the cell is to survive. In most tissues this inactivity is maintained by the constant supply to the cell of a large number of chemical "survival signals" provided by neighboring cells, hormones, and the extracellular matrix. In other words, most cells are programmed to commit suicide if survival signals are not received from the internal environment. For example, prostate-gland cells undergo apoptosis when the influence on them of testosterone, the male sex hormone, is removed. In addition, there are other chemical signals, some exogenous to the organism (for example, certain viruses and bacterial toxins) and some endogenous (for example, certain messengers released by nerve cells and white blood cells) that can inhibit or override survival signals and induce the cell to undergo apoptosis.

It is very likely that abnormal inhibition of appropriate apoptosis may contribute to diseases, like cancer, characterized by excessive numbers of cells. At the other end of the spectrum, too high a rate of apopto-sis probably contributes to degenerative diseases, such as that of bone in the disease called osteoporosis. The hope is that therapies designed to enhance or decrease apoptosis, depending on the situation, would ameliorate these diseases.

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Essentials of Human Physiology

Essentials of Human Physiology

This ebook provides an introductory explanation of the workings of the human body, with an effort to draw connections between the body systems and explain their interdependencies. A framework for the book is homeostasis and how the body maintains balance within each system. This is intended as a first introduction to physiology for a college-level course.

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